Platelet glycoprotein Ibα forms catch bonds with human WT vWF but not with type 2B von Willebrand disease vWF

PubMed Central

Yago, Tadayuki; Lou, Jizhong; Wu, Tao; Yang, Jun; Miner, Jonathan J.; Coburn, Leslie; López, José A.; Cruz, Miguel A.; Dong, Jing-Fei; McIntire, Larry V.; McEver, Rodger P.; Zhu, Cheng

2008-01-01

Arterial blood flow enhances glycoprotein Ibα (GPIbα) binding to vWF, which initiates platelet adhesion to injured vessels. Mutations in the vWF A1 domain that cause type 2B von Willebrand disease (vWD) reduce the flow requirement for adhesion. Here we show that increasing force on GPIbα/vWF bonds first prolonged (“catch”) and then shortened (“slip”) bond lifetimes. Two type 2B vWD A1 domain mutants, R1306Q and R1450E, converted catch bonds to slip bonds by prolonging bond lifetimes at low forces. Steered molecular dynamics simulations of GPIbα dissociating from the A1 domain suggested mechanisms for catch bonds and their conversion by the A1 domain mutations. Catch bonds caused platelets and GPIbα-coated microspheres to roll more slowly on WT vWF and WT A1 domains as flow increased from suboptimal levels, explaining flow-enhanced rolling. Longer bond lifetimes at low forces eliminated the flow requirement for rolling on R1306Q and R1450E mutant A1 domains. Flowing platelets agglutinated with microspheres bearing R1306Q or R1450E mutant A1 domains, but not WT A1 domains. Therefore, catch bonds may prevent vWF multimers from agglutinating platelets. A disintegrin and metalloproteinase with a thrombospondin type 1 motif–13 (ADAMTS-13) reduced platelet agglutination with microspheres bearing a tridomain A1A2A3 vWF fragment with the R1450E mutation in a shear-dependent manner. We conclude that in type 2B vWD, prolonged lifetimes of vWF bonds with GPIbα on circulating platelets may allow ADAMTS-13 to deplete large vWF multimers, causing bleeding. PMID:18725999

Modifying murine von Willebrand factor A1 domain for in vivo assessment of human platelet therapies.

PubMed

Chen, Jianchun; Tan, Kui; Zhou, Hairu; Lo, Hsuan-Fu; Tronik-Le Roux, Diana; Liddington, Robert C; Diacovo, Thomas G

2008-01-01

The A1 domain of von Willebrand factor (VWF-A1) plays a crucial role in hemostasis and thrombosis by initiating platelet adhesion at sites of arterial injury through interactions with the platelet receptor glycoprotein Ib alpha (GPIbalpha). Here we report that murine VWF-A1 supports limited binding of human platelets. However, atomic models of GPIbalpha-VWF-A1 complexes identified an electrostatic 'hot-spot' that, when mutated in murine VWF-A1, switches its binding specificity from mouse to human GPIbalpha. Furthermore, mice expressing this mutant VWF-A1 display a bleeding phenotype that can be corrected by infusion of human platelets. Mechanistically, human platelets correct the phenotype by forming occlusive thrombi, an event that can be abrogated by blockade of GPIbalpha or by the preadministration of inhibitors of platelet activation or adhesion (clopidogrel (Plavix) and abciximab (ReoPro), respectively). Thus, by modifying a protein interface, we have generated a potential biological platform for preclinical screening of antithrombotics that specifically target human platelets.

From grand-canonical density functional theory towards rational compound design

NASA Astrophysics Data System (ADS)

von Lilienfeld, Anatole

2008-03-01

The fundamental challenge of rational compound design, ie the reverse engineering of chemical compounds with predefined specific properties, originates in the high-dimensional combinatorial nature of chemical space. Chemical space is the hyper-space of a given set of molecular observables that is spanned by the grand-canonical variables (particle densities of electrons and nuclei) which define chemical composition. A brief but rigorous description of chemical space within the molecular grand-canonical ensemble multi-component density functional theory framework will be given [1]. Numerical results will be presented for intermolecular energies as a continuous function of alchemical variations within a neutral and isoelectronic 10 proton system, including CH4, NH3, H2O, and HF, interacting with formic acid [2]. Furthermore, engineering the Fermi level through alchemical generation of boron-nitrogen doped mutants of benzene shall be discussed [3].[1] von Lilienfeld and Tuckerman JCP 125 154104 (2006)[2] von Lilienfeld and Tuckerman JCTC 3 1083 (2007)[3] Marcon et al. JCP 127 064305 (2007)

Safety and Suitability for Service Assessment Testing for Shoulder Launched Munitions

DTIC Science & Technology

2014-11-07

Registrierung und Auswertung von Waffen -und Detonationsknallen 31 Motor Case Burst Probability ARO Report 75-2, SMC-S-001 Def Stan 07-85 32...détonation Vorschriften und Richtlinien zur Registrierung und Auswertung von Waffen und Detonationsknallen and STANAG 4569 with references...l’exploitation des bruits d’armes et des bruits de détonation Vorschriften und Richtlinien zur Registrierung und Auswertung von Waffen und

Wernher von Braun

NASA Image and Video Library

1964-03-24

Marshall Space Flight Center Director Dr. Wernher von Braun presents Lady Bird Johnson with an inscribed hard hat during the First Lady's March 24, 1964 visit. While at the Marshall Center, Mrs. Johnson addressed Center employees, toured facilities and witnessed test firings of a Saturn I first stage and an F-1 engine. Dr. von Braun is wearing a Texas hat presented to him months earlier by Lyndon Johnson during a visit to the Johnson ranch in Texas.

Segmentierung von Aortenaneurysmen in CTA-Bildern mit dem statistischen Verfahren der Active Appearance Models

NASA Astrophysics Data System (ADS)

Greiner, Katharina; Egger, Jan; Großkopf, Stefan; Kaftan, Jens N.; Dörner, Ralf; Freisleben, Bernd

In diesem Beitrag werden Active Appearance Models (AAMs) zur Segmentierung der äußeren Kontur von Aortenaneurysmen eingesetzt. Diese Aufgabe ist wegen des geringen Kontrastes zum umliegenden Gewebe und des Aufbaus der teils thrombotisierten oder kalzifizierten Gefäßwände im Bereich eines Aneurysmas so komplex, dass sie aufgrund der Vielgestalt der Kontur in CT-Angiographie-Bildern die Verwendung eines statistischen Modells für Form und eingeschlossene Textur rechtfertigt. Für die Evaluation des Verfahrens wurden verschiedene statistische Modelle aus Schichten von neun CTA-Datensätzen trainiert und die Segmentierung anhand von Leave-One-Out-Tests überprüft.

Deep soil compaction as a method of ground improvement and to stabilization of wastes and slopes with danger of liquefaction, determining the modulus of deformation and shear strength parameters of loose rock.

PubMed

Lersow, M

2001-01-01

For the stabilization of dumps with the construction of hidden dams and for building ground improvement, for instance for traffic lines over dumps, nearly all applied compaction methods have the aim to reduce the pore volume in the loose rock. With these methods, a homogenization of the compacted loose rock will be obtained too. The compaction methods of weight compaction by falling weight, compaction by vibration and compaction by blasting have been introduced, and their applications and efficiencies have been shown. For the estimation of the effective depth of the compaction and for a safe planning of the bearing layer, respectively, the necessary material parameters have to be determined for each deep compaction method. Proposals for the determination of these parameters have been made within this paper. In connection with the stabilization of flow-slide-prone dump slopes, as well as for the improvement of dump areas for the use as building ground, it is necessary to assess the deformation behavior and the bearing capacity. To assess the resulting building ground improvement, deformation indexes (assessment of the flow-prone layer) and strength indexes (assessment of the bearing capacity) have to be determined with soil mechanical tests. Förster and Lersow, [Patentschrift DE 197 17 988. Verfahren, auf der Grundlage last- und/oder weggesteuerter Plattendruckversuche auf der Bohrlochsohle, zur Ermittlung des Spannungs-Verformungs-Verhaltens und/oder von Deformationsmoduln und/oder von Festigkeitseigenschaften in verschiedenen Tiefen insbesondere von Lockergesteinen und von Deponiekörpern in situ; Förster W, Lersow M. Plattendruckversuch auf der Bohrlochsohle, Ermittlung des Spannungs-Verformungs-Verhaltens von Lockergestein und Deponiematerial Braunkohle--Surface Mining, 1998;50(4): 369-77; Lersow M. Verfahren zur Ermittlung von Scherfestigkeitsparametern von Lockergestein und Deponiematerial aus Plattendruckversuchen auf der Bohrlochsohle. Braunkohle--Surface Mining, 1995;51(1):39-47] improved a direct procedure, the so-called plate-loading test. With this improved procedure, it is possible to produce profiles of deformation parameters and shear-strength parameters of the loose rock. On this basis the settlement behavior and the bearing behavior of the ground can be described. The PDV-BS cone-penetration test and the pressiometer test are compared and the reliability of the soil mechanical indexes are assessed critically. The PDV-BS can be used as a calibration test for cone penetration tests as well as for the calibration of pressiometer tests. With the application of a PDV-BS and a pressiometer test in combination in a testing field, the anisotropy properties of the loose rock can be proved.

Molecular-genetic diagnostics of von Hippel-Lindau syndrome (VHL) in Bulgaria: first complex mutation event in the VHL gene.

PubMed

Glushkova, Maria; Dimova, Petia; Yordanova, Iglika; Todorov, Tihomir; Tourtourikov, Ivan; Mitev, Vanyo; Todorova, Albena

2018-02-01

Von Hippel-Lindau syndrome is an autosomal-dominant disease characterized by the formation of various tumours and cysts in many different parts of the body. Von Hippel-Lindau syndrome is caused by VHL gene mutations leading to production of impaired tumor suppressor Von Hippel-Lindau syndrome protein or its complete absence. To study five patients with clinically suspected Von Hippel-Lindau syndrome, who were referred for molecular genetic testing. Sanger sequencing of the coding regions of the VHL gene. Five clinically relevant germline mutations were detected. One of the pathogenic variants has not been previously reported. This novel mutation is a complex mutation event combining a duplication and an indel, rearranging exon 3 of the VHL gene - c. [516_517dupGTCAAGCCT; 532_542delCTGGACATCGTinsATTA], p. (Glu173Serfs*4). Overall, our results showed that the diagnosis of Von Hippel-Lindau syndrome in our country is difficult most probably because of its heterogeneous clinical manifestation and insufficient knowledge on the diagnostic criteria for the disease. From genetic point of view our results add some novel data on the mutation profile of the VHL gene. In order to prove or revise the diagnosis, early genetic testing is strongly recommended in affected patients and their family members to ensure appropriate follow-up and treatment of the malignancies.

Test of Von Baer's law of the conservation of early development.

PubMed

Poe, Steven

2006-11-01

One of the oldest and most pervasive ideas in comparative embryology is the perceived evolutionary conservation of early ontogeny relative to late ontogeny. Karl Von Baer first noted the similarity of early ontogeny across taxa, and Ernst Haeckel and Charles Darwin gave evolutionary interpretation to this phenomenon. In spite of a resurgence of interest in comparative embryology and the development of mechanistic explanations for Von Baer's law, the pattern itself has been largely untested. Here, I use statistical phylogenetic approaches to show that Von Baer's law is an unnecessarily complex explanation of the patterns of ontogenetic timing in several clades of vertebrates. Von Baer's law suggests a positive correlation between ontogenetic time and amount of evolutionary change. I compare ranked position in ontogeny to frequency of evolutionary change in rank for developmental events and find that these measures are not correlated, thus failing to support Von Baer's model. An alternative model that postulates that small changes in ontogenetic rank are evolutionarily easier than large changes is tentatively supported.

Sex differences in mechanical allodynia: how can it be preclinically quantified and analyzed?

PubMed Central

Nicotra, Lauren; Tuke, Jonathan; Grace, Peter M.; Rolan, Paul E.; Hutchinson, Mark R.

2014-01-01

Translating promising preclinical drug discoveries to successful clinical trials remains a significant hurdle in pain research. Although animal models have significantly contributed to understanding chronic pain pathophysiology, the majority of research has focused on male rodents using testing procedures that produce sex difference data that do not align well with comparable clinical experiences. Additionally, the use of animal pain models presents ongoing ethical challenges demanding continuing refinement of preclinical methods. To this end, this study sought to test a quantitative allodynia assessment technique and associated statistical analysis in a modified graded nerve injury pain model with the aim to further examine sex differences in allodynia. Graded allodynia was established in male and female Sprague Dawley rats by altering the number of sutures placed around the sciatic nerve and quantified by the von Frey test. Linear mixed effects modeling regressed response on each fixed effect (sex, oestrus cycle, pain treatment). On comparison with other common von Frey assessment techniques, utilizing lower threshold filaments than those ordinarily tested, at 1 s intervals, appropriately and successfully investigated female mechanical allodynia, revealing significant sex and oestrus cycle difference across the graded allodynia that other common behavioral methods were unable to detect. Utilizing this different von Frey approach and graded allodynia model, a single suture inflicting less allodynia was sufficient to demonstrate exaggerated female mechanical allodynia throughout the phases of dioestrus and pro-oestrus. Refining the von Frey testing method, statistical analysis technique and the use of a graded model of chronic pain, allowed for examination of the influences on female mechanical nociception that other von Frey methods cannot provide. PMID:24592221

Vertical bending strength and torsional rigidity analysis of formula student car chassis

NASA Astrophysics Data System (ADS)

Hazimi, Hashfi; Ubaidillah, Setiyawan, Adi Eka Putra; Ramdhani, Hanief Cahya; Saputra, Murnanda Zaesy; Imaduddin, Fitrian

2018-02-01

Formula Society of Automotive Engineers (FSAE) is a competition for students to construct formula student car. One of an essential part of a formula student car is its chassis. Chassis is an internal vehicle frame which holds all another part of the vehicle and secures the driver. The team have to design their chassis and tests their design to achieve the best chassis that fulfill the regulation. This paper contains chassis design from Bengawan FSAE Team and some FEA tests to find out the Tensile Strength, Torsional Rigidity, and Von Misses Stress of Formula SAE car. Torsional rigidity was found by applying the static torsional test. The results from torsional rigidity test are a maximum deformation of 9.9512 mm with 1.7064 safety factor, and 35.935 MPa maximum Von Misses Stress. Moreover, then the result of the vertical bending strength test is 8.1214 mm max deformation with safety factor 4.2717, and 29.226 MPa maximum Von Misses Stress.

Abschätzung des Einflusses von Parameterunsicherheiten bei der Planung und Auswertung von Tracertests unter Verwendung von Ensembleprognosen

NASA Astrophysics Data System (ADS)

Klotzsch, Stephan; Binder, Martin; Händel, Falk

2017-06-01

While planning tracer tests, uncertainties in geohydraulic parameters should be considered as an important factor. Neglecting these uncertainties can lead to missing the tracer breakthrough, for example. One way to consider uncertainties during tracer test design is the so called ensemble forecast. The applicability of this method to geohydrological problems is demonstrated by coupling the method with two analytical solute transport models. The algorithm presented in this article is suitable for prediction as well as parameter estimation. The parameter estimation function can be used in a tracer test for reducing the uncertainties in the measured data which can improve the initial prediction. The algorithm was implemented into a software tool which is freely downloadable from the website of the Institute for Groundwater Management at TU Dresden, Germany.

A Test Fixture for Detecting the Presence of Water in Buoyant Cables

DTIC Science & Technology

1990-06-14

Systems Branch, along with Messrs. Craig L. Flynn, Eric von Winkle and Phillip Watrous of the Pressure Lab for their assistance in the measurements...Report No. 4051; 2 April 1971, p. 110. [7] Tareev, B. Physics of Dielectrics. (Moscow, USSR: Mir Publishers, 1979), pp. 116- 134. [81 von Hippel , A.R...34 Telephony, August 10, 1981; pp. 58 - 60, 149. Von Hippel , Arthur R. Dielectrics and Waves. (New York: John Wiley and Sons, 1954). Wentworth, F.L. and M. Cohn

Wernher von Braun

NASA Image and Video Library

1958-01-31

Jet Propulsion Laboratory Director Dr. James Pickering, Dr. James van Allen of the State University of Iowa, and Army Ballistic missionile Agency Technical Director Dr. Wernher von Braun triumphantly display a model of the Explorer I, America's first satellite, shortly after the satellite's launch on January 31, 1958. The Jet Propulsion Laboratory packed and tested the payload, a radiation detection experiment designed by Dr. van Allen. Dr. von Braun's rocket team at Redstone Arsenal in Huntsville, Alabama, developed the Juno I launch vehicle, a modified Jupiter-C.

Wernher von Braun

NASA Image and Video Library

1968-10-01

Dr. von Braun inside the KC-135 in flight. The KC-135 provide NASA's Reduced-Gravity Program the unique weightlessness or zero-g environment of space flight for testing and training of human and hardware reactions. The recent version, KC-135A, is a specially modified turbojet transport which flies parabolic arcs to produce weightlessness periods of 20 to 25 seconds and its cargo bay test area is approximately 60 feet long, 10 feet wide, and 7 feet high.

Color constancy: enhancing von Kries adaption via sensor transformations

NASA Astrophysics Data System (ADS)

Finlayson, Graham D.; Drew, Mark S.; Funt, Brian V.

1993-09-01

Von Kries adaptation has long been considered a reasonable vehicle for color constancy. Since the color constancy performance attainable via the von Kries rule strongly depends on the spectral response characteristics of the human cones, we consider the possibility of enhancing von Kries performance by constructing new `sensors' as linear combinations of the fixed cone sensitivity functions. We show that if surface reflectances are well-modeled by 3 basis functions and illuminants by 2 basis functions then there exists a set of new sensors for which von Kries adaptation can yield perfect color constancy. These new sensors can (like the cones) be described as long-, medium-, and short-wave sensitive; however, both the new long- and medium-wave sensors have sharpened sensitivities -- their support is more concentrated. The new short-wave sensor remains relatively unchanged. A similar sharpening of cone sensitivities has previously been observed in test and field spectral sensitivities measured for the human eye. We present simulation results demonstrating improved von Kries performance using the new sensors even when the restrictions on the illumination and reflectance are relaxed.

Platelet-free shear flow assay facilitates analysis of shear-dependent functions of VWF and ADAMTS13.

PubMed

Kraus, Emma; Kraus, Kristina; Obser, Tobias; Oyen, Florian; Klemm, Ulrike; Schneppenheim, Reinhard; Brehm, Maria A

2014-12-01

The multimeric form of von Willebrand factor (VWF), is the largest soluble protein in mammals and exhibits a multidomain structure resulting in multiple functions. Upon agonist stimulation endothelial cells secrete VWF multimers from Weibel-Palade bodies into the blood stream where VWF plays an essential role in platelet-dependent primary hemostasis. Elongation of VWF strings on the cells' surface leads to accessibility of VWF binding sites for proteins, such as platelet membrane glycoprotein Ib. The prothrombotic strings are size-regulated by the metalloprotease ADAMTS13 by shear force-activated proteolytic cleavage. VWF string formation was induced by histamine stimulation of HUVEC cells under unidirectional shear flow and VWF strings were detected employing the VWF binding peptide of platelet glycoprotein Ib coupled to latex beads. VWF strings were then used as substrate for kinetic studies of recombinant and plasma ADAMTS13. To investigate specific aspects of the shear-dependent functions of VWF and ADAMTS13, we developed a shear flow assay that allows observation of VWF string formation and their degradation by ADAMTS13 without the need for isolated platelets. Our assay specifically detects VWF strings, can be coupled with fluorescent applications and allows semi-automated, quantitative assessment of recombinant and plasma ADAMTS13 activity. Our assay may serve as a valuable research tool to investigate the biochemical characteristics of VWF and ADAMTS13 under shear flow and could complement diagnostics of von Willebrand Disease and Thrombotic Thrombocytopenic Purpura as it allows detection of shear flow-dependent dysfunction of VWD-associated VWF mutants as well as TTP-associated ADAMTS13 mutants. Copyright © 2014 Elsevier Ltd. All rights reserved.

Coats' disease, Turner syndrome, and von Willebrand disease in a patient with Wildtype Norrie disease pseudoglioma.

PubMed

Desai, Rajen U; Saffra, Norman A; Krishna, Rati P; Rosenberg, Steven E

2011-01-01

The authors describe a girl diagnosed as having Coats' disease, Turner syndrome (45X karyotype), and type 1 von Willebrand disease. She tested negative for the Norrie disease pseudoglioma (NDP) gene located on the X-chromosome, which has been suspected of contributing to Coats' disease. Copyright 2010, SLACK Incorporated.

mRNAs for PRPs, statherin, and histatins in von Ebner's gland tissues.

PubMed

Azen, E A; Hellekant, G; Sabatini, L M; Warner, T F

1990-11-01

A search was made for expression of genes for proline-rich proteins (PRPs) and other salivary-type proteins, including statherin and histatins, in taste-bud tissues of mice and primates because of previous genetic findings in mice (Azen et al., 1986) that Prp and taste genes for certain bitter substances are either the same or closely linked. Taste-bud tissues and other tissues were tested for specific mRNAs with labeled DNA probes by Northern blotting and in situ hybridization. It was found that PRP mRNAs were present in von Ebner's glands of mice and macaques, and that there was a much greater degree of PRP mRNA induction in mouse parotid (16-fold) than in von Ebner's gland (two-fold) after in vivo isoproterenol stimulation. This difference may be due, in part, to differences in autonomic nerve innervation. Statherin and histatin mRNAs were found in macaque taste-bud tissues containing von Ebner's gland, and statherin protein was found in human von Ebner's gland by immunohistochemistry. The finding of PRP gene expression in von Ebner's gland, whose secretions have been suggested to play a role in taste stimulation, adds further support to a possible function of PRPs in bitter tasting. The possible functions of statherin and histatins in von Ebner's gland secretions may be related to statherin's regulation of salivary calcium and histatins' antibacterial and antifungal properties.

Hydrostatic Stress Effect On the Yield Behavior of Inconel 100

NASA Technical Reports Server (NTRS)

Allen, Phillip A.; Wilson, Christopher D.

2002-01-01

Classical metal plasticity theory assumes that hydrostatic stress has no effect on the yield and postyield behavior of metals. Recent reexaminations of classical theory have revealed a significant effect of hydrostatic stress on the yield behavior of notched geometries. New experiments and nonlinear finite element analyses (FEA) of Inconel 100 (IN 100) equal-arm bend and double-edge notch tension (DENT) test specimens have revealed the effect of internal hydrostatic tensile stresses on yielding. Nonlinear FEA using the von Mises (yielding is independent of hydrostatic stress) and the Drucker-Prager (yielding is linearly dependent on hydrostatic stress) yield functions was performed. In all test cases, the von Mises constitutive model, which is independent of hydrostatic pressure, overestimated the load for a given displacement or strain. Considering the failure displacements or strains, the Drucker-Prager FEMs predicted loads that were 3% to 5% lower than the von Mises values. For the failure loads, the Drucker Prager FEMs predicted strains that were 20% to 35% greater than the von Mises values. The Drucker-Prager yield function seems to more accurately predict the overall specimen response of geometries with significant internal hydrostatic stress influence.

Inattentional blindness and the von Restorff effect.

PubMed

Schmidt, Stephen R; Schmidt, Constance R

2015-02-01

Sometimes we fail to notice distinctive or unusual items (inattentional blindness), while other times we remember distinctive items more than expected items (the von Restorff effect). A three-factor framework is presented and tested in two experiments in an attempt to reconcile these seemingly contradictory phenomena. Memory for different types of unexpected stimuli was tested after an easy or difficult Stroop color-naming task. Highly arousing taboo words were well remembered even when the difficult Stroop task limited attentional resources. However, a conceptual isolation effect was only observed when the nature of the category change was highlighted by the Stroop task, the Stroop task was easy, and/or the isolated targets enjoyed a retrieval advantage relative to comparison targets. As proposed in the three-factor framework, the arousing qualities of the stimuli, the attentional demands of the primary task, and the relevance of isolated features at encoding and retrieval combine to produce inattentional blindness and the von Restorff effect.

Von Gierke disease

MedlinePlus

... liver or kidney Blood sugar test Genetic testing Lactic acid blood test Triglyceride level Uric acid blood ... sugar and high levels of lactate (produced from lactic acid), blood fats (lipids), and uric acid.

Conventional Rapid Latex Agglutination in Estimation of von Willebrand Factor: Method Revisited and Potential Clinical Applications

PubMed Central

Che Hussin, Che Maraina

2014-01-01

Measurement of von Willebrand factor antigen (VWF : Ag) levels is usually performed in a specialised laboratory which limits its application in routine clinical practice. So far, no commercial rapid test kit is available for VWF : Ag estimation. This paper discusses the technical aspect of latex agglutination method which was established to suit the purpose of estimating von Willebrand factor (VWF) levels in the plasma sample. The latex agglutination test can be performed qualitatively and semiquantitatively. Reproducibility, stability, linearity, limit of detection, interference, and method comparison studies were conducted to evaluate the performance of this test. Semiquantitative latex agglutination test was strongly correlated with the reference immunoturbidimetric assay (Spearman's rho = 0.946, P < 0.001, n = 132). A substantial agreement (κ = 0.77) was found between qualitative latex agglutination test and the reference assay. Using the scoring system for the rapid latex test, no agglutination is with 0% VWF : Ag (control negative), 1+ reaction is equivalent to <20% VWF : Ag, and 4+ reaction indicates >150% VWF : Ag (when comparing with immunoturbidimetric assay). The findings from evaluation studies suggest that latex agglutination method is suitable to be used as a rapid test kit for the estimation of VWF : Ag levels in various clinical conditions associated with high levels and low levels of VWF : Ag. PMID:25759835

Expression of connective tissue growth factor (CTGF/CCN2) in breast cancer cells is associated with increased migration and angiogenesis.

PubMed

Chien, Wenwen; O'Kelly, James; Lu, Daning; Leiter, Amanda; Sohn, Julia; Yin, Dong; Karlan, Beth; Vadgama, Jay; Lyons, Karen M; Koeffler, H Phillip

2011-06-01

Connective tissue growth factor (CTGF/CCN2) belongs to the CCN family of matricellular proteins, comprising Cyr61, CTGF, NovH and WISP1-3. The CCN proteins contain an N-terminal signal peptide followed by four conserved domains sharing sequence similarities with the insulin-like growth factor binding proteins, von Willebrand factor type C repeat, thrombospondin type 1 repeat, and a C-terminal growth factor cysteine knot domain. To investigate the role of CCN2 in breast cancer, we transfected MCF-7 cells with full-length CCN2, and with four mutant constructs in which one of the domains had been deleted. MCF-7 cells stably expressing full-length CCN2 demonstrated reduced cell proliferation, increased migration in Boyden chamber assays and promoted angiogenesis in chorioallantoic membrane assays compared to control cells. Deletion of the C-terminal cysteine knot domain, but not of any other domain-deleted mutants, abolished activities mediated by full-length CCN2. We have dissected the role of CCN2 in breast tumorigenesis on a structural basis.

Experimente ueber den Einflusse von Metabolites und Antimetaboliten am Modell von Trichomonas Vaginalis. III. Mitteilung: Experimente mit Essentiellen Fettsaeuren (Experiments on the Influence of Metabolites and Antimetabolites on the Model of Trichomonas Vaginalis. III. Communication: Experiments with Essential Fatty Acids),

DTIC Science & Technology

The relationship between the double and trifold unsaturated fatty acids and Trichomonas vaginalis was tested. The experiments aimed at testing the...influence of vitamin F, linolic and linoleic acid upon multiplication of Trichomonas vaginalis . Vitamin F exerts trichomonacidal effect upon... Trichomonas vaginalis cultures. Linolic acid alone does not yet show great differences at concentrations of 0,01 to 0.05 mg/ml, as compared to the controls. At

Novel Thrombotic Function of a Human SNP in STXBP5 Revealed by CRISPR/Cas9 Gene Editing in Mice.

PubMed

Zhu, Qiuyu Martin; Ko, Kyung Ae; Ture, Sara; Mastrangelo, Michael A; Chen, Ming-Huei; Johnson, Andrew D; O'Donnell, Christopher J; Morrell, Craig N; Miano, Joseph M; Lowenstein, Charles J

2017-02-01

To identify and characterize the effect of a SNP (single-nucleotide polymorphism) in the STXBP5 locus that is associated with altered thrombosis in humans. GWAS (genome-wide association studies) have identified numerous SNPs associated with human thrombotic phenotypes, but determining the functional significance of an individual candidate SNP can be challenging, particularly when in vivo modeling is required. Recent GWAS led to the discovery of STXBP5 as a regulator of platelet secretion in humans. Further clinical studies have identified genetic variants of STXBP5 that are linked to altered plasma von Willebrand factor levels and thrombosis in humans, but the functional significance of these variants in STXBP5 is not understood. We used CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated 9) techniques to produce a precise mouse model carrying a human coding SNP rs1039084 (encoding human p. N436S) in the STXBP5 locus associated with decreased thrombosis. Mice carrying the orthologous human mutation (encoding p. N437S in mouse STXBP5) have lower plasma von Willebrand factor levels, decreased thrombosis, and decreased platelet secretion compared with wild-type mice. This thrombosis phenotype recapitulates the phenotype of humans carrying the minor allele of rs1039084. Decreased plasma von Willebrand factor and platelet activation may partially explain the decreased thrombotic phenotype in mutant mice. Using precise mammalian genome editing, we have identified a human nonsynonymous SNP rs1039084 in the STXBP5 locus as a causal variant for a decreased thrombotic phenotype. CRISPR/Cas9 genetic editing facilitates the rapid and efficient generation of animals to study the function of human genetic variation in vascular diseases. © 2016 American Heart Association, Inc.

von Willebrand Factor Test

MedlinePlus

... Cancer Therapy Glucose Tests Gonorrhea Testing Gram Stain Growth Hormone Haptoglobin hCG Pregnancy hCG Tumor Marker HDL Cholesterol ... Semen Analysis Serotonin Serum Free Light Chains Sex Hormone Binding Globulin ... Transferrin Receptor Stool Culture Stool Elastase Strep ...

Genetic and Pharmacological Strategies to Refunctionalize the von Hippel Lindau R167Q Mutant Protein

PubMed Central

Ding, Zhiyong; German, Peter; Bai, Shanshan; Reddy, A. Srinivas; Liu, Xian-De; Sun, Mianen; Zhou, Lijun; Chen, Xiaohua; Zhao, Xiaobei; Wu, Chengbiao; Zhang, Shuxing; Mills, Gordon B.; Jonasch, Eric

2014-01-01

Aberrant von Hippel Lindau (VHL) protein function is the underlying driver of VHL-related diseases, including both sporadic and inherited clear cell renal cell carcinoma (ccRCC). About one third of VHL mutations are missense point mutations, with R167Q being the most common VHL point mutation in hereditary VHL disease. Although it has been studied extensively, the ability of VHL-R167Q to downregulate hypoxia inducible factor 2α (HIF2α) is still controversial. In addition, the manner in which the mutation contributes to tumorigenesis is not fully understood. No therapeutic approach is available to target VHL-R167Q and similar missense point mutations. We analyzed VHL-R167Q proteostasis and function at normoxia, at hypoxia with different oxygen pressure, and in a xenograft mouse model. We showed that the protein levels of VHL-R167Q dictate its ability to downregulate HIF2α and suppress tumor growth. Strikingly, the proteasome inhibitors bortezomib and carfilzomib, which are currently in clinical use, stabilize VHL-R167Q and increase its ability to downregulate HIF2α. VHL-R167Q binds elongin C and elongin B with considerably less avidity than wild-type VHL does but retains residual capacity to generate a VHL-elongin C-elongin B complex, downregulate HIF2α, and suppress tumorigenesis, which could be rescued by increase VHL-R167Q levels. Finally, we used in silico approaches and identified other missense VHL mutants in addition to VHL-R167Q that might be rescued by similar strategies. Thus, our studies revealed detailed information describing how VHL-R167Q contributes to tumorigenesis and identified a potential targeted therapy for ccRCC and other VHL-related disease in patients carrying VHL-R167Q or similar missense mutations. PMID:24755468

Functional Assessment of Laser Irradiation.

DTIC Science & Technology

1988-03-01

shock altogether. Following shaping, threshold acuity testing was derived using a modification of the von Bekesy tracking technique (14). In this...burns produced by atomic flash. AMA Arch. Ophthal 53: 351-364 (1955) 2. Hawerth, R.S. and Sperling , H.G. Prolonged color blindness induced by intense...Swinnen, M.E.T., Brady, J.V. & Powell, M.G. A new device for the application of shock. Behav. Meth. & Instrum 1: 184 (1969) 14. Bekesy, G. von . A new

Experimente ueber den Einflusse von Metaboliten und Antimetaboliten am Modell von Trichomonas Vaginalis. IX. Mitteilung: Experimente mit Enzymen (Experiments on the Influence of Metabolites and Antimetabolites on the Model of Trichomonas Vaginalis. IX. Communication: Experiments on Enzymes),

DTIC Science & Technology

some enzymes to trichomonas. The following enzymes were used for experiment: pepsin, trypsin, distaste, urease and lysozyme. Tests were performed...obtained in the experiments with urease . Trichomonas growth under addition of lysozyme was within the range of the control cultures. (Modified author abstract)

Glucocorticoids promote Von Hippel Lindau degradation and Hif-1α stabilization

PubMed Central

Greenald, David; Wilson, Garrick K.; Peron, Margherita; Markham, Eleanor; Sinnakaruppan, Mathavan; Matthews, Laura C.; McKeating, Jane A.; Argenton, Francesco; van Eeden, Fredericus J. M.

2017-01-01

Glucocorticoid (GC) and hypoxic transcriptional responses play a central role in tissue homeostasis and regulate the cellular response to stress and inflammation, highlighting the potential for cross-talk between these two signaling pathways. We present results from an unbiased in vivo chemical screen in zebrafish that identifies GCs as activators of hypoxia-inducible factors (HIFs) in the liver. GCs activated consensus hypoxia response element (HRE) reporters in a glucocorticoid receptor (GR)-dependent manner. Importantly, GCs activated HIF transcriptional responses in a zebrafish mutant line harboring a point mutation in the GR DNA-binding domain, suggesting a nontranscriptional route for GR to activate HIF signaling. We noted that GCs increase the transcription of several key regulators of glucose metabolism that contain HREs, suggesting a role for GC/HIF cross-talk in regulating glucose homeostasis. Importantly, we show that GCs stabilize HIF protein in intact human liver tissue and isolated hepatocytes. We find that GCs limit the expression of Von Hippel Lindau protein (pVHL), a negative regulator of HIF, and that treatment with the c-src inhibitor PP2 rescued this effect, suggesting a role for GCs in promoting c-src–mediated proteosomal degradation of pVHL. Our data support a model for GCs to stabilize HIF through activation of c-src and subsequent destabilization of pVHL. PMID:28851829

Von Willebrand's disease: case report and review of literature.

PubMed

Echahdi, Hanae; El Hasbaoui, Brahim; El Khorassani, Mohamed; Agadr, Aomar; Khattab, Mohamed

2017-01-01

Von Willebrand Disease (VWD) is the most common human inherited bleeding disorder due to a defect of Von Willebrand Factor (VWF), which a glycoprotein crucial for platelet adhesion to the subendothelium after vascular injury. VWD include quantitative defects of VWF, either partial (type 1 with VWF levels < 50 IU/dL) or virtually total (type 3 with undetectable VWF levels) and also qualitative defects of VWF (type 2 variants with discrepant antigenic and functional VWF levels). The most bleeding forms of VWD usually do not concern type 1 patients with the mildest VWF defects (VWF levels between 30 and 50IU/dL). Von willebrand factor is a complex multimeric protein with two functions: it forms a bridge between the platelets and areas of vascular damage and it binds to and stabilizes factor VIII, which is necessary for the clotting cascade. By taking a clinical history of bleeding (mucocutaneous bleeding symptoms suggestive of a primary haemostatic disorder, a quantitative or qualitative abnormality of VWF is possible) it is important to think about VWD and to make the appropriate diagnosis. If the VWD is suspected diagnostic tests should include an activated partial thromboplastin time, bleeding time, factor VIII: C Ristocetin cofactor and vWF antigen. Additional testing of ristocetin induced plattlet adhesion (RIPA) the multimeric structure and collagen binding test and genanalysis allow diagnosing the different types of von. Willebrand Disease. The treatment of choice in mild forms is the synthetic agent desmopressin. In patients with severe type 1, type 2B, 2N and type 3 or in people who do not response to desmopressin, the appropriate treatment is a factor VIII concentrate that is rich of VWF. We report a case of infant in 27-month-old boy who had been referred due to haemorrhagic shock. His birth histories, his familie's social history and developmental milestones were unremarkable. He was born at full term with no antenatal or perinatal complications. Prior to the symptoms, the child was on a normal diet and was thriving appropriately. The child presented one days before his admission trauma to the inner face of the lower lip that caused an external acute bleeding loss. The laboratory data showed unfortunately, the most severe form of Von Willebrand's Disease; Type 3. The management was based on erythrocyte and fresh-frozen plasma (FFP) transfusions with administration of factor VII with good evolution.

Hepatologie Neuere Forschungsergebnisse in ihrer Bedeutung für das Verständnis von Leberkrankheiten

NASA Astrophysics Data System (ADS)

Gerok, W.; Blum, H. E.; Offensperger, W.; Offensperger, S.; Andus, T.; Groß, V.; Heinrich, P. C.

1991-06-01

By two exemplary clinical situations — acute viral hepatitis, acute-phase reaction of the liver — the significance of basic research for the understanding of clinical phenomena and for the development of new diagnostic and therapeutic procedures is demonstrated. The very different phenomena following infection with the hepatitis-B-virus can be explained by the variation in the interactions of virus and liver cell, by the immune reaction of the host, and by mutants of the virus. The reaction of the liver to an extrahepatic infection is mediated by interleukin-6, and characterized by an alteration in protein metabolism. The synthesis of acute-phase proteins is increased. The proteins confine the local injury and establish the homeostasis of the organism.

Effects of Turbulence Model and Numerical Time Steps on Von Karman Flow Behavior and Drag Accuracy of Circular Cylinder

NASA Astrophysics Data System (ADS)

Amalia, E.; Moelyadi, M. A.; Ihsan, M.

2018-04-01

The flow of air passing around a circular cylinder on the Reynolds number of 250,000 is to show Von Karman Vortex Street Phenomenon. This phenomenon was captured well by using a right turbulence model. In this study, some turbulence models available in software ANSYS Fluent 16.0 was tested to simulate Von Karman vortex street phenomenon, namely k- epsilon, SST k-omega and Reynolds Stress, Detached Eddy Simulation (DES), and Large Eddy Simulation (LES). In addition, it was examined the effect of time step size on the accuracy of CFD simulation. The simulations are carried out by using two-dimensional and three- dimensional models and then compared with experimental data. For two-dimensional model, Von Karman Vortex Street phenomenon was captured successfully by using the SST k-omega turbulence model. As for the three-dimensional model, Von Karman Vortex Street phenomenon was captured by using Reynolds Stress Turbulence Model. The time step size value affects the smoothness quality of curves of drag coefficient over time, as well as affecting the running time of the simulation. The smaller time step size, the better inherent drag coefficient curves produced. Smaller time step size also gives faster computation time.

Von Hippel-Lindau Syndrome

MedlinePlus

... examination to look for retinal tumors, beginning around age 2 Yearly physical examination Yearly blood test and/or 24-hour urine test to screen for elevated catecholamines, beginning around age 5 Yearly abdominal ultrasound to look at the ...

Non-Destructive Impermeability Testing of Land-Based Sewage Systems (zerstoerungsfreie dichtheitspruefung con grundstuecksentwaesserungsleitungen)

DTIC Science & Technology

2001-01-01

CYberdeckungsh6he zunehmen. Ffr die Stabilitdt des Str ~mungszustandes ist dagegen ein weniger empfindlicher Ansaugstutzen von Vorteil, weil geringe Schwankungen im...Gerinnestr() mung mit einem Laser-Doppler- Anemometer und einem Pitot-Rohr Ltd. BD Dipl.-Ing. B. Ftirmaier M6glichkeiten der Verwertung von HausmUll und...GrundstticksentwAsserungsleitungen ISBN 3-486-26517-2 * diese Hefte k6nnen beim Oldenbourg Industrieverlag GmbH, Rosenheimer Str . 145, 81671 MUnchen bezogen werden (Preis pro Heft: 35,00 DM, Stand 2001)

Use of Topical PC-NSAIDs to Treat Burn Injury and Pain

DTIC Science & Technology

2017-10-01

termination of the study. At days 3, 5, 10 and 15 post-burn, the animals were again tested for sensitivity to a stimulus (von Frey hair of varying stiffness...special cages so that one hind paw was exposed to stimulations with up to eight different force von Frey hairs using the Dixon up/down method. The...broken dermal structures such as capillaries, some hair shafts, and ducts, This observation of increased sub dermal HBD-1 has been reported previously as

Vaccine Protection of Leukopenic Mice against Staphylococcus aureus Bloodstream Infection

PubMed Central

Rauch, Sabine; Gough, Portia; Kim, Hwan Keun; Schneewind, Olaf

2014-01-01

The risk for Staphylococcus aureus bloodstream infection (BSI) is increased in immunocompromised individuals, including patients with hematologic malignancy and/or chemotherapy. Due to the emergence of antibiotic-resistant strains, designated methicillin-resistant S. aureus (MRSA), staphylococcal BSI in cancer patients is associated with high mortality; however, neither a protective vaccine nor pathogen-specific immunotherapy is currently available. Here, we modeled staphylococcal BSI in leukopenic CD-1 mice that had been treated with cyclophosphamide, a drug for leukemia and lymphoma patients. Cyclophosphamide-treated mice were highly sensitive to S. aureus BSI and developed infectious lesions lacking immune cell infiltrates. Virulence factors of S. aureus that are key for disease establishment in immunocompetent hosts—α-hemolysin (Hla), iron-regulated surface determinants (IsdA and IsdB), coagulase (Coa), and von Willebrand factor binding protein (vWbp)—are dispensable for the pathogenesis of BSI in leukopenic mice. In contrast, sortase A mutants, which cannot assemble surface proteins, display delayed time to death and increased survival in this model. A vaccine with four surface antigens (ClfA, FnBPB, SdrD, and SpAKKAA), which was identified by genetic vaccinology using sortase A mutants, raised antigen-specific immune responses that protected leukopenic mice against staphylococcal BSI. PMID:25183728

Neurocognitive profile of a young adolescent with DK phocomelia/von Voss phocomelia/von Voss Cherstvoy syndrome.

PubMed

Antonini, Tanya N; Van Horn Kerne, Valerie; Axelrad, Marni E; Karaviti, Lefkothea P; Schwartz, David D

2015-07-01

DK phocomelia/von Voss Cherstvoy syndrome is a rare condition characterized by upper limb and urogenital abnormalities and various brain anomalies. Previously reported cases have noted significant developmental delays, although no formal testing of cognitive abilities has been reported. In this paper we describe results from a comprehensive neuropsychological evaluation of a 12-year-old male with DK phocomelia syndrome. Test findings indicated mild impairment in intellectual functioning, with more significant impairment in adaptive skills and academic achievement. The neuropsychological profile converged with neurological findings, showing a distinct pattern of strengths and weaknesses that suggests functional compromise of posterior brain regions with relatively well-preserved functioning of more anterior regions. Specifically, impairments were evident in perceptual reasoning, visual perception, and visuomotor integration, whereas normal or near normal functioning was evident in memory, receptive language, social cognition, attention, and most aspects of executive functioning. To our knowledge this is the first report to describe the neurocognitive profile of an individual with DK phocomelia syndrome. © 2015 Wiley Periodicals, Inc.

Experimente ueber den Einflusse von Metaboliten und Antimetaboliten am Model von Trichomonas Vaginalis. II. Mitteilung: Experimente mit der Vitamin K-Gruppe (Experiments on the Influence of Metabolites and Antimetabolites on the Model of Trichomonas Vaginalis. II. Communication: Experiments with the Vitamin K-Group),

DTIC Science & Technology

K4 essential reduction of multiplication of Trichomonas vaginalis was observed within a range of 0.25 and 0.35 mg/ml, from 0.40 mg/ml onward single...The aim of the investigation was to test the relationship between the individual K-vitamins K1, K3, K4 and K5 and Trichomonas analytically. The...show any remarkable differences between the control culture and the test series (Table 1) in Trichomonas multiplication. With vitamin K3 gradually

Platelet Disorders: MedlinePlus Health Topic

MedlinePlus

... von Willebrand Factor Test (American Association for Clinical Chemistry) What Are Bone Marrow Tests? (National Heart, Lung, and Blood Institute) Treatments and Therapies Splenectomy (Mayo Foundation for Medical Education and Research) Also in Spanish What Is a Blood Transfusion? ( ...

Problem-Solving Test: Tryptophan Operon Mutants

ERIC Educational Resources Information Center

Szeberenyi, Jozsef

2010-01-01

This paper presents a problem-solving test that deals with the regulation of the "trp" operon of "Escherichia coli." Two mutants of this operon are described: in mutant A, the operator region of the operon carries a point mutation so that it is unable to carry out its function; mutant B expresses a "trp" repressor protein unable to bind…

Potential misdiagnosis of von Willebrand disease and haemophilia caused by ineffective mixing of thawed plasma.

PubMed

Favaloro, E J; Oliver, S; Mohammed, S; Ahuja, M; Grzechnik, E; Azimulla, S; McDonald, J; Lima-Oliveira, G; Lippi, G

2017-09-01

von Willebrand disease (VWD) reflects a loss or dysfunction in von Willebrand factor (VWF), while haemophilia represents a loss or dysfunction of clotting factors such as factor VIII (FVIII) or FIX. Their diagnosis requires laboratory testing, with this potentially compromised by preanalytical events, including poor sample quality. This study assessed the effect of inadequate mixing as a potential cause of VWD and haemophilia misdiagnosis. After completion of requested testing, 48 consecutive patient samples comprising separate aliquots from single collections were individually pooled, appropriately mixed, then frozen in separate aliquots, either at -20°C or -80°C for 2-7 days. Each sample set was then thawed and the separate aliquots subjected to separate mixing protocols (several inversions, blood roller, vortex) vs a non-mix sample, and all aliquots then tested for various VWF and factor assays. Non-mixing led to substantial reduction in VWF and factors in about 25% of samples, that in some cases could lead to misdiagnosis of VWD or haemophilia. Interestingly, there were also some differences observed with respect to different mixing protocols. Our study identified ineffective or variable mixing of thawed plasma samples as potential causes of misdiagnosis of VWD or haemophilia. Further education regarding the importance of appropriate mixing appears warranted. © 2017 John Wiley & Sons Ltd.

Diagnosis and management of von Willebrand disease: a developing country perspective.

PubMed

Nair, Sukesh Chandran; Viswabandya, Auro; Srivastava, Alok

2011-07-01

Special challenges exist in the management of patients with von Willebrand disease (VWD) because of limitations in diagnostic facilities and therapeutic options. However, even within these limitations, it is possible to establish comprehensive services for this condition. Our data show that among 202 patients with VWD, 107 were type 3, 62 were type 1, and the others different categories of type 2. Basic tests such as bleeding time and activated partial thromboplastin time with factor (F)VIII coagulant are able to diagnose most of those with severe disease. We have been able to adapt the specific tests such as von Willebrand factor (VWF) ristocetin cofactor and VWF antigen from the tedious batched manual methods to cost-effective automated methods on advanced coagulometers. Discriminatory tests such as VWF collagen binding, VWF:FVIIIB, ristocetin-induced platelet agglutination (RIPA) are done in batches. Therapeutic options and for the treatment of bleeding include desmopressin, cryoprecipitate, and intermediate purity VWF-containing clotting factor concentrates. Tranexamic acid is also widely used as well as hormonal therapy for menorrhagia. We have also shown that modest doses of intermediate purity FVIII (Koate DVI; Talecris Biotherapeutics, Raleigh, NC, USA) at 35 IU/kg preoperatively and 10 to 20 IU/kg after that are sufficient for surgical hemostasis in these patients. © Thieme Medical Publishers.

Pretest 3D finite element analysis of the WIPP Intermediate Scale Borehole Test

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arguello, J.G.

A three dimensional pretest finite element analysis of the Intermediate Scale Borehole Test has been performed. In the analysis, the 7.7 years simulation period includes the mining of Rooms C1 and C2, and the N1420 cross drift, at time zero; drilling of the borehole between the two rooms at 5.7 years; and 2 years of post-drilling response. An all salt configuration was used in the calculation. The 1984 Waste Isolation Pilot Plant (WIPP) reference elastic-secondary creep law, with reduced elastic moduli, was used to model the creeping response of the salt. Results show that after mining of the rooms andmore » cross drift a relatively high von Mises stress state exists around the perimeter of the pillar. However, by 5.7 years, or immediately prior to drilling of the borehole, the pillar has relaxed to an almost uniform von Mises stress of about 7--8 MPa. After the borehole is drilled, a relatively high von Mises stress field is once again set up in the immediate vicinity of the hole. This drives the creep closure of the borehole. The hole closes more in the vertical direction than in the horizontal direction, resulting in ovalling of the hole. At the end of the simulation, the von Mises stress around the borehole is still higher than that in the remained of the pillar. Thus, the closure rates are relatively high at the end of the simulation time.« less

Zu einer inhaltsorientierten Theorie des Lernens und Lehrens der biologischen Evolution

NASA Astrophysics Data System (ADS)

Wallin, Anita

Der Zweck dieser Studie (zwecks Überblick siehe dazu Abb. 9.1) war zu untersuchen, wie die Schüler der Sekundarstufe II ein Verständnis von der Theorie der biologischen Evolution entwickeln. Vom Ausgangspunkt "Vorurteile der Schüler“ ausgehend wurden Unterrichtssequenzen entwickelt und drei verschiedene Lernexperimente in einem zyklischen Prozess durchgeführt. Das Wissen der Schüler wurde vor, während und nach den Unterrichtssequenzen mit Hilfe von schriftlichen Tests, Interviews und Diskussionsrunden in kleinen Gruppen abgefragt. Etwa 80 % der Schüler hatten vor dem Unterricht alternative Vorstellungen von Evolution, und in dem Nachfolgetest erreichten circa 75 % ein wissenschaftliches Niveau. Die Argumentation der Schüler in den verschiedenen Tests wurde sorgfältig unter Rücksichtnahme auf Vorurteile, der konzeptionellen Struktur der Theorie der Evolution und den Zielen des Unterrichts analysiert. Daraus konnten Einsichten in solche Anforderungen an Lehren und Lernen gewonnen werden, die Herausforderungen an Schüler und Lehrer darstellen, wenn sie anfangen, evolutionäre Biologie zu lernen oder zu lehren. Ein wichtiges Ergebnis war, dass das Verständnis existierender Variation in einer Population der Schlüssel zum Verständnis von natürlicher Selektion ist. Die Ergebnisse sind in einer inhaltsorientierten Theorie zusammengefasst, welche aus drei verschiedenen Aspekten besteht: 1) den inhaltsspezifischen Aspekten, die einzigartig für jedes wissenschaftliche Feld sind; 2) den Aspekten, die die Natur der Wissenschaft betreffen; und 3) den allgemeinen Aspekten. Diese Theorie kann in neuen Experimenten getestet und weiter entwickelt werden.

Generalization of von Neumann analysis for a model of two discrete half-spaces: The acoustic case

USGS Publications Warehouse

Haney, M.M.

2007-01-01

Evaluating the performance of finite-difference algorithms typically uses a technique known as von Neumann analysis. For a given algorithm, application of the technique yields both a dispersion relation valid for the discrete time-space grid and a mathematical condition for stability. In practice, a major shortcoming of conventional von Neumann analysis is that it can be applied only to an idealized numerical model - that of an infinite, homogeneous whole space. Experience has shown that numerical instabilities often arise in finite-difference simulations of wave propagation at interfaces with strong material contrasts. These interface instabilities occur even though the conventional von Neumann stability criterion may be satisfied at each point of the numerical model. To address this issue, I generalize von Neumann analysis for a model of two half-spaces. I perform the analysis for the case of acoustic wave propagation using a standard staggered-grid finite-difference numerical scheme. By deriving expressions for the discrete reflection and transmission coefficients, I study under what conditions the discrete reflection and transmission coefficients become unbounded. I find that instabilities encountered in numerical modeling near interfaces with strong material contrasts are linked to these cases and develop a modified stability criterion that takes into account the resulting instabilities. I test and verify the stability criterion by executing a finite-difference algorithm under conditions predicted to be stable and unstable. ?? 2007 Society of Exploration Geophysicists.

A double commutant theorem for Murray–von Neumann algebras

PubMed Central

Liu, Zhe

2012-01-01

Murray–von Neumann algebras are algebras of operators affiliated with finite von Neumann algebras. In this article, we study commutativity and affiliation of self-adjoint operators (possibly unbounded). We show that a maximal abelian self-adjoint subalgebra of the Murray–von Neumann algebra associated with a finite von Neumann algebra is the Murray–von Neumann algebra , where is a maximal abelian self-adjoint subalgebra of and, in addition, is . We also prove that the Murray–von Neumann algebra with the center of is the center of the Murray–von Neumann algebra . Von Neumann’s celebrated double commutant theorem characterizes von Neumann algebras as those for which , where , the commutant of , is the set of bounded operators on the Hilbert space that commute with all operators in . At the end of this article, we present a double commutant theorem for Murray–von Neumann algebras. PMID:22543165

A novel deletion mutation is recurrent in von Willebrand disease types 1 and 3.

PubMed

Sutherland, Megan S; Cumming, Anthony M; Bowman, Mackenzie; Bolton-Maggs, Paula H B; Bowen, Derrick J; Collins, Peter W; Hay, Charles R M; Will, Andrew M; Keeney, Stephen

2009-07-30

Direct sequencing of VWF genomic DNA in 21 patients with type 3 von Willebrand disease (VWD) failed to reveal a causative homozygous or compound heterozygous VWF genotype in 5 cases. Subsequent analysis of VWF mRNA led to the discovery of a deletion (c.221-977_532 + 7059del [p.Asp75_Gly178del]) of VWF in 7 of 12 white type 3 VWD patients from 6 unrelated families. This deletion of VWF exons 4 and 5 was absent in 9 patients of Asian origin. We developed a genomic DNA-based assay for the deletion, which also revealed its presence in 2 of 34 type 1 VWD families, segregating with VWD in an autosomal dominant fashion. The deletion was associated with a specific VWF haplotype, indicating a possible founder origin. Expression studies indicated markedly decreased secretion and defective multimerization of the mutant VWF protein. Further studies have found the mutation in additional type 1 VWD patients and in a family expressing both type 3 and type 1 VWD. The c.221-977_532 + 7059del mutation represents a previously unreported cause of both types 1 and 3 VWD. Screening for this mutation in other type 1 and type 3 VWD patient populations is required to elucidate further its overall contribution to VWD arising from quantitative deficiencies of VWF.

A simplified up-down method (SUDO) for measuring mechanical nociception in rodents using von Frey filaments

PubMed Central

2014-01-01

Background The measurement of mechanosensitivity is a key method for the study of pain in animal models. This is often accomplished with the use of von Frey filaments in an up-down testing paradigm. The up-down method described by Chaplan et al. (J Neurosci Methods 53:55–63, 1994) for mechanosensitivity testing in rodents remains one of the most widely used methods for measuring pain in animals. However, this method results in animals receiving a varying number of stimuli, which may lead to animals in different groups receiving different testing experiences that influences their later responses. To standardize the measurement of mechanosensitivity we developed a simplified up-down method (SUDO) for estimating paw withdrawal threshold (PWT) with von Frey filaments that uses a constant number of five stimuli per test. We further refined the PWT calculation to allow the estimation of PWT directly from the behavioral response to the fifth stimulus, omitting the need for look-up tables. Results The PWT estimates derived using SUDO strongly correlated (r > 0.96) with the PWT estimates determined with the conventional up-down method of Chaplan et al., and this correlation remained very strong across different levels of tester experience, different experimental conditions, and in tests from both mice and rats. The two testing methods also produced similar PWT estimates in prospective behavioral tests of mice at baseline and after induction of hyperalgesia by intraplantar capsaicin or complete Freund’s adjuvant. Conclusion SUDO thus offers an accurate, fast and user-friendly replacement for the widely used up-down method of Chaplan et al. PMID:24739328

Complexion of forces in an anisotropic self-gravitating system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kandrup, H.E.

Chandrasekhar and von Neumann developed a completely stochastic formalism to analyze the complexion of forces acting upon a test star situated in an infinite, homogeneous distribution of field stars. This formalism is generalized here to allow for more realistic inhomogeneous and anisotropic systems. It is demonstrated that the forces acting upon a test star decompose ''naturally'' into the incoherent sum of a mean force associated with the average spatial inhomogeneity and a fluctuating force associated with stochastic deviations from these mean conditions. Moreover, as in the special case considered by Chandrasekhar and von Neumann, one can apparently associate the fluctuatingmore » forces with the effects of particularly proximate field stars, thereby motivating the ''nearest neighbor'' interpretation first introduced by Chandrasekhar.« less

Molecular and clinical profile of von Willebrand disease in Spain (PCM-EVW-ES): comprehensive genetic analysis by next-generation sequencing of 480 patients

PubMed Central

Borràs, Nina; Batlle, Javier; Pérez-Rodríguez, Almudena; López-Fernández, María Fernanda; Rodríguez-Trillo, Ángela; Lourés, Esther; Cid, Ana Rosa; Bonanad, Santiago; Cabrera, Noelia; Moret, Andrés; Parra, Rafael; Mingot-Castellano, María Eva; Balda, Ignacia; Altisent, Carme; Pérez-Montes, Rocío; Fisac, Rosa María; Iruín, Gemma; Herrero, Sonia; Soto, Inmaculada; de Rueda, Beatriz; Jiménez-Yuste, Víctor; Alonso, Nieves; Vilariño, Dolores; Arija, Olga; Campos, Rosa; Paloma, María José; Bermejo, Nuria; Berrueco, Rubén; Mateo, José; Arribalzaga, Karmele; Marco, Pascual; Palomo, Ángeles; Sarmiento, Lizheidy; Iñigo, Belén; Nieto, María del Mar; Vidal, Rosa; Martínez, María Paz; Aguinaco, Reyes; César, Jesús María; Ferreiro, María; García-Frade, Javier; Rodríguez-Huerta, Ana María; Cuesta, Jorge; Rodríguez-González, Ramón; García-Candel, Faustino; Cornudella, Rosa; Aguilar, Carlos; Vidal, Francisco; Corrales, Irene

2017-01-01

Molecular diagnosis of patients with von Willebrand disease is pending in most populations due to the complexity and high cost of conventional molecular analyses. The need for molecular and clinical characterization of von Willebrand disease in Spain prompted the creation of a multicenter project (PCM-EVW-ES) that resulted in the largest prospective cohort study of patients with all types of von Willebrand disease. Molecular analysis of relevant regions of the VWF, including intronic and promoter regions, was achieved in the 556 individuals recruited via the development of a simple, innovative, relatively low-cost protocol based on microfluidic technology and next-generation sequencing. A total of 704 variants (237 different) were identified along VWF, 155 of which had not been previously recorded in the international mutation database. The potential pathogenic effect of these variants was assessed by in silico analysis. Furthermore, four short tandem repeats were analyzed in order to evaluate the ancestral origin of recurrent mutations. The outcome of genetic analysis allowed for the reclassification of 110 patients, identification of 37 asymptomatic carriers (important for genetic counseling) and re-inclusion of 43 patients previously excluded by phenotyping results. In total, 480 patients were definitively diagnosed. Candidate mutations were identified in all patients except 13 type 1 von Willebrand disease, yielding a high genotype-phenotype correlation. Our data reinforce the capital importance and usefulness of genetics in von Willebrand disease diagnostics. The progressive implementation of molecular study as the first-line test for routine diagnosis of this condition will lead to increasingly more personalized and effective care for this patient population. PMID:28971901

Molecular and clinical profile of von Willebrand disease in Spain (PCM-EVW-ES): comprehensive genetic analysis by next-generation sequencing of 480 patients.

PubMed

Borràs, Nina; Batlle, Javier; Pérez-Rodríguez, Almudena; López-Fernández, María Fernanda; Rodríguez-Trillo, Ángela; Lourés, Esther; Cid, Ana Rosa; Bonanad, Santiago; Cabrera, Noelia; Moret, Andrés; Parra, Rafael; Mingot-Castellano, María Eva; Balda, Ignacia; Altisent, Carme; Pérez-Montes, Rocío; Fisac, Rosa María; Iruín, Gemma; Herrero, Sonia; Soto, Inmaculada; de Rueda, Beatriz; Jiménez-Yuste, Víctor; Alonso, Nieves; Vilariño, Dolores; Arija, Olga; Campos, Rosa; Paloma, María José; Bermejo, Nuria; Berrueco, Rubén; Mateo, José; Arribalzaga, Karmele; Marco, Pascual; Palomo, Ángeles; Sarmiento, Lizheidy; Iñigo, Belén; Nieto, María Del Mar; Vidal, Rosa; Martínez, María Paz; Aguinaco, Reyes; César, Jesús María; Ferreiro, María; García-Frade, Javier; Rodríguez-Huerta, Ana María; Cuesta, Jorge; Rodríguez-González, Ramón; García-Candel, Faustino; Cornudella, Rosa; Aguilar, Carlos; Vidal, Francisco; Corrales, Irene

2017-12-01

Molecular diagnosis of patients with von Willebrand disease is pending in most populations due to the complexity and high cost of conventional molecular analyses. The need for molecular and clinical characterization of von Willebrand disease in Spain prompted the creation of a multicenter project (PCM-EVW-ES) that resulted in the largest prospective cohort study of patients with all types of von Willebrand disease. Molecular analysis of relevant regions of the VWF , including intronic and promoter regions, was achieved in the 556 individuals recruited via the development of a simple, innovative, relatively low-cost protocol based on microfluidic technology and next-generation sequencing. A total of 704 variants (237 different) were identified along VWF , 155 of which had not been previously recorded in the international mutation database. The potential pathogenic effect of these variants was assessed by in silico analysis. Furthermore, four short tandem repeats were analyzed in order to evaluate the ancestral origin of recurrent mutations. The outcome of genetic analysis allowed for the reclassification of 110 patients, identification of 37 asymptomatic carriers (important for genetic counseling) and re-inclusion of 43 patients previously excluded by phenotyping results. In total, 480 patients were definitively diagnosed. Candidate mutations were identified in all patients except 13 type 1 von Willebrand disease, yielding a high genotype-phenotype correlation. Our data reinforce the capital importance and usefulness of genetics in von Willebrand disease diagnostics. The progressive implementation of molecular study as the first-line test for routine diagnosis of this condition will lead to increasingly more personalized and effective care for this patient population. Copyright© 2017 Ferrata Storti Foundation.

Transfusion medicine management for reconstructive spinal repair in a patient with von Willebrand's disease and a history of heavy surgical bleeding.

PubMed

Bolan, C D; Rick, M E; Polly, D W

2001-12-01

A case report of a multidisciplinary approach to a second reconstructive back surgery in a patient with von Willebrand's disease, flatback syndrome, and a history of heavy surgical bleeding is presented. To review the perioperative planning and assessment of hemostasis and transfusion medicine management, including administration of Humate P, a Factor VIII preparation with high von Willebrand factor content. Reconstructive spinal procedures may require significant transfusion support even in patients with normal preoperative hemostasis. In addition to the hemostatic problem caused by von Willebrand's disease, the reported patient requested minimal exposure to allogeneic blood products because of hepatitis C infection acquired from previous transfusions. The multidisciplinary team included the patient, hematologist, blood bank medical director, anesthesiologist, and operating surgeon. Preoperative assessment showed a Type 2A von Willebrand's disease variant. A careful planning process included a test infusion of desmopressin and extensive autologous donations of red cells, plasma, and platelets, which were collected before the procedure. Anterior and posterior spine fusions were performed during a 14-hour procedure. Hemostasis and clinical response were excellent. Humate P was administered perioperatively as assessed by the baseline Factor VIII and von Willebrand's disease levels, the plasma volume, the half-life of infused Humate P, and the anticipated risk and tolerance for bleeding. The estimated blood loss was 5 L. Replacement included 9 units of autologous red cells, 6 units of autologous plasma, 2 autologous plateletpheresis collections, a single allogeneic plateletpheresis product, and 17,000 units of Humate P administered over the perioperative period. Using a careful multidisciplinary approach, excellent hemostasis can be achieved with minimal exposure to untreated allogeneic blood products during aggressive spinal surgery in a patient with a clinically significant congenital coagulopathy.

Empirical Evaluation of Directional-Dependence Tests

ERIC Educational Resources Information Center

Thoemmes, Felix

2015-01-01

Testing of directional dependence is a method to infer causal direction that recently has attracted some attention. Previous examples by e.g. von Eye and DeShon (2012a) and extensive simulation studies by Pornprasertmanit and Little (2012) have demonstrated that under specific assumptions, directional-dependence tests can recover the true causal…

Congenital Type III von Willebrand's disease unmasked by hypothyroidism in a Shetland sheepdog.

PubMed

Scuderi, Margaret; Bessey, Lauren; Snead, Elisabeth; Burgess, Hilary; Carr, Anthony

2015-09-01

A 7-year-old, spayed female Shetland sheepdog had sudden onset of right-sided epistaxis. Diagnostic tests revealed Type III von Willebrand's disease and primary hypothyroidism leading to an acute hypothyroid crisis and acquired factor VIII (FVIII) deficiency. Levothyroxine therapy normalized the serum thyroxine and FVIII concentrations. The delayed onset of disease and the reversible FVIII deficiency that was corrected with levothyroxine therapy, support a role for hypothyroidism in the pathogenesis of this dog's sudden bleeding tendency as has been seen with hypothyroidism in humans.

Congenital Type III von Willebrand’s disease unmasked by hypothyroidism in a Shetland sheepdog

PubMed Central

Scuderi, Margaret; Bessey, Lauren; Snead, Elisabeth; Burgess, Hilary; Carr, Anthony

2015-01-01

A 7-year-old, spayed female Shetland sheepdog had sudden onset of right-sided epistaxis. Diagnostic tests revealed Type III von Willebrand’s disease and primary hypothyroidism leading to an acute hypothyroid crisis and acquired factor VIII (FVIII) deficiency. Levothyroxine therapy normalized the serum thyroxine and FVIII concentrations. The delayed onset of disease and the reversible FVIII deficiency that was corrected with levothyroxine therapy, support a role for hypothyroidism in the pathogenesis of this dog’s sudden bleeding tendency as has been seen with hypothyroidism in humans. PMID:26347307

A Modified Cramer-von Mises and Anderson-Darling Test for the Weibull Distribution with Unknown Location and Scale Parameters.

DTIC Science & Technology

1981-12-01

preventing the generation of 16 6 negative location estimators. Because of the invariant pro- perty of the EDF statistics, this transformation will...likelihood. If the parameter estimation method developed by Harter and Moore is used, care must be taken to prevent the location estimators from being...vs A 2 Critical Values, Level-.Ol, n-30 128 , 0 6N m m • w - APPENDIX E Computer Prgrams 129 Program to Calculate the Cramer-von Mises Critical Values

Functional characterisation of the type 1 von Willebrand disease candidate VWF gene variants: p.M771I, p.L881R and p.P1413L

PubMed Central

Berber, Ergul; Ozbil, Mehmet; Brown, Christine; Baslar, Zafer; Caglayan, S. Hande; Lillicrap, David

2017-01-01

Background Abnormalities in the biosynthetic pathway or increased clearance of plasma von Willebrand factor (VWF) are likely to contribute to decreased plasma VWF levels in inherited type 1 von Willebrand disease (VWD). Recent studies demonstrated that 65% of type 1 VWD patients have candidate VWF mutations, the majority of which are missense variants. The purpose of this study was to explore the effects of three VWF missense mutations (p.M771I, p.L881R and p.P1413L) located in different functional domains of VWF, reported as candidate mutations in type 1 VWD patients in the course of the MCMDM-1VWD study. Materials and methods The focus of these studies was on the intracellular biosynthetic processing and localisation of VWF in a heterologous cell system. Molecular dynamic simulation for p.M771I and p.P1413L was also performed to analyse the conformational effects of the changes. Results As determined by immunofluorescence antibody staining and confocal microscopy of HEK293 cells, the intracellular localisation of recombinant VWF with the p.M771I variation was impaired. Transient transfection studies and phorbol myristate acetate stimulation in COS-7 cells revealed significant intracellular retention. In addition, major loss of VWF multimers was observed for only the p.M771I mutation. Molecular dynamic simulations on p.M771I mutant VWF revealed distinct structural rearrangements including a large deviation in the E’ domain, and significant loss of β-sheet secondary structure. Discussion The pathogenic effects of candidate VWF gene mutations were explored in this study. In vitro expression studies in heterologous cell systems revealed impaired secretion of VWF and a dominant negative effect on the processing of the wild-type protein for only the p.M771I mutation and none of the mutations affected the regulated secretion. PMID:27483487

Functional characterisation of the type 1 von Willebrand disease candidate VWF gene variants: p.M771I, p.L881R and p.P1413L.

PubMed

Berber, Ergul; Ozbil, Mehmet; Brown, Christine; Baslar, Zafer; Caglayan, S Hande; Lillicrap, David

2017-10-01

Abnormalities in the biosynthetic pathway or increased clearance of plasma von Willebrand factor (VWF) are likely to contribute to decreased plasma VWF levels in inherited type 1 von Willebrand disease (VWD). Recent studies demonstrated that 65% of type 1 VWD patients have candidate VWF mutations, the majority of which are missense variants. The purpose of this study was to explore the effects of three VWF missense mutations (p.M771I, p.L881R and p.P1413L) located in different functional domains of VWF, reported as candidate mutations in type 1 VWD patients in the course of the MCMDM-1VWD study. The focus of these studies was on the intracellular biosynthetic processing and localisation of VWF in a heterologous cell system. Molecular dynamic simulation for p.M771I and p.P1413L was also performed to analyse the conformational effects of the changes. As determined by immunofluorescence antibody staining and confocal microscopy of HEK293 cells, the intracellular localisation of recombinant VWF with the p.M771I variation was impaired. Transient transfection studies and phorbol myristate acetate stimulation in COS-7 cells revealed significant intracellular retention. In addition, major loss of VWF multimers was observed for only the p.M771I mutation. Molecular dynamic simulations on p.M771I mutant VWF revealed distinct structural rearrangements including a large deviation in the E' domain, and significant loss of β-sheet secondary structure. The pathogenic effects of candidate VWF gene mutations were explored in this study. In vitro expression studies in heterologous cell systems revealed impaired secretion of VWF and a dominant negative effect on the processing of the wild-type protein for only the p.M771I mutation and none of the mutations affected the regulated secretion.

Gerbstoffe aus Potentilla officinalis wirken entzündungshemmend im UV-Erythem-Test und bei Anwendung auf atopischer Haut.

PubMed

Hoffmann, Julia; Wölfle, Ute; Schempp, Christoph M; Casetti, Federica

2016-09-01

Das Rhizom von Potentilla officinalis (PO) ist reich an Gerbstoffen und wird traditionell zur äußerlichen Behandlung von Entzündungen der Haut und der Schleimhäute verwendet. Ziel der vorliegenden Arbeit war die Bestätigung der antiinflammatorischen Eigenschaften von PO mittels eines UV-Erythem-Tests und einer klinischen Anwendungsstudie bei atopischer Haut. Die antiinflammatorische Wirkung eines PO-Extrakts (standardisiert auf 2 % Trockensubstanz) wurde in einer prospektiven, randomisierten, placebokontrollierten Doppelblindstudie mit 40 gesunden Erwachsenen im UV-Erythem-Test im Vergleich zu 1 % Hydrocortisonacetat untersucht. Im Rahmen einer prospektiven nicht kontrollierten Studie wurde die Wirkung und Verträglichkeit der 2 % PO-Creme an zwölf Erwachsenen und zwölf Kindern mit atopischer Haut nach Anwendung über zwei Wochen in einem definierten Testareal anhand eines Teil-SCORAD untersucht. Zusätzlich wurde die Beeinflussung der Hautrötung im Testareal photometrisch gemessen. Im UV-Erythem-Test zeigte die PO-Creme eine signifikante Reduktion des Erythemindex im Vergleich zum Vehikel. Die antiinflammatorische Wirkung des Verums entsprach der der 1 % Hydrocortisonacetat-Creme. Die klinische Studie bei Atopikern zeigte eine signifikante Abnahme des Teil-SCORAD und des Erythems im Testareal. Es wurden keine Unverträglichkeitsreaktionen beobachtet. PO als 2%ige Zubereitung besitzt entzündungshemmende Eigenschaften und ist wirksam und gut verträglich auf atopischer Haut. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Von Hippel-Lindau Disease

MedlinePlus

What is Von Hippel-Lindau disease (VHL)? Von Hippel-Lindau disease (VHL) is a rare disease that causes tumors and cysts to grow in your body. They ... can become cancerous. What causes Von Hippel-Lindau disease (VHL)? Von Hippel-Lindau disease (VHL) is a ...

Remission of recurrent gastrointestinal bleeding after septal reduction therapy in patients with hypertrophic obstructive cardiomyopathy-associated acquired von Willebrand syndrome.

PubMed

Blackshear, J L; Stark, M E; Agnew, R C; Moussa, I D; Safford, R E; Shapiro, B P; Waldo, O A; Chen, D

2015-02-01

Gastrointestinal hemorrhage is considered to be a severe complication of von Willebrand disease. The optimal therapy for acquired von Willebrand syndrome and severe gastrointestinal bleeding with hypertrophic cardiomyopathy is undefined. Seventy-seven patients (median age, 67 years; interquartile range [IQR], 56-75 years; 49% women) with hypertrophic cardiomyopathy underwent von Willebrand factor multimer testing and acquisition of bleeding history. Bleeding was detected in 27 (36%) (median age, 74 years; IQR 66-76 years; 74% women), 20 with gastrointestinal bleeding, including 11 women with transfusion dependence. In these 11 women, the median duration of transfusion dependency was 36 months (IQR 18-44 months), and the median number of transfusions required was 25 (IQR 20-38). Two patients had undergone bowel resection for bleeding, one of them twice. Seven patients showed angiodysplasia, and the remainder had no endoscopic lesion. Bleeding recurred after bowel surgery or endoscopic intervention and medical therapy for hypertrophic cardiomyopathy in 10 of 11 patients. Two patients had septal myectomy, and six patients underwent alcohol septal ablation. With the exception of one patient in whom a significant gradient persisted after septal ablation, after the periprocedural period, patients after septal reduction therapy remained free of recurrent bleeding and need for transfusions. Acquired von Willebrand syndrome is common in hypertrophic cardiomyopathy. Gastrointestinal bleeding often recurs after endoscopic therapy, but may be relieved by structural cardiac repair. © 2014 International Society on Thrombosis and Haemostasis.

IPS-Empress II inlay-retained fixed partial denture reinforced with zirconia bar: three-dimensional finite element and in-vitro studies.

PubMed

Kermanshah, Hamid; Geramy, Allahyar; Ebrahimi, Shahram Farzin; Bitaraf, Tahereh

2012-12-01

This study evaluated von Mises stress distribution, flexural strength and interface micrographs of IPS-Empress II (IPS) inlay-retained fixed partial dentures (IRFPD) reinforced with Zirconia bars (Zb). In the Finite element analysis, six three-dimensional models of IRFPD were designed using Solid Works 2006. Five models were reinforced with different Zb and a model without Zb was considered as a control. The bridges were loaded by 200 and 500 N forces at the middle of the pontic on the occlusal surface. Subsequently, von Mises stress and displacement of the models were evaluated along a defined path. In the experimental part, 21 bar shape specimens were fabricated from lithium disilicate and zirconia ceramic in three different designs. The zirconia-IPS interfaces and the fractured surfaces of flexural test were observed using SEM. In the connector area, von Mises stress and displacement of the models with Zb under a load of 500 N were decreased compared to the model without the Zb; however, this difference was not considerable at a load of 200 N. In the mesial connector, Von Mises stress and displacement was decreased from 12.5 Mpa for the control model tested at 500 N to 7.0 Mpa for the model with Zb and from 0.0050-0.0041 mm, respectively. SEM analyses showed that, before fracture, interfacial gaps were not observed along the interfaces, but initiated cracks propagated along the interfaces after flexural loading. IPS IRFPD reinforced by Zb can tolerate higher stresses while still functioning effectively and the interfaces may have desirable adaption.

PT2385 for the Treatment of Von Hippel-Lindau Disease-Associated Clear Cell Renal Cell Carcinoma

ClinicalTrials.gov

2017-08-23

VHL Gene Mutation; VHL; VHL Syndrome; VHL Gene Inactivation; Von Hippel; Von Hippel-Lindau Disease; Von Hippel's Disease; Von Hippel-Lindau Syndrome, Modifiers of; Clear Cell Renal Cell Carcinoma; Clear Cell RCC; ccRCC

Walt Disney visited Marshall Space Flight Center (MSFC)

NASA Technical Reports Server (NTRS)

1965-01-01

Walt Disney toured the West Test Area during his visit to the Marshall Space Flight Center on April 13, 1965. The three in center foreground are Karl Heimburg, Director, Test Division; Dr. von Braun, Director, MSFC; and Walt Disney. The Dynamic Test Stand with the S-1C stage being installed is in the background.

Functional display of platelet-binding VWF fragments on filamentous bacteriophage.

PubMed

Yee, Andrew; Tan, Fen-Lai; Ginsburg, David

2013-01-01

von Willebrand factor (VWF) tethers platelets to sites of vascular injury via interaction with the platelet surface receptor, GPIb. To further define the VWF sequences required for VWF-platelet interaction, a phage library displaying random VWF protein fragments was screened against formalin-fixed platelets. After 3 rounds of affinity selection, DNA sequencing of platelet-bound clones identified VWF peptides mapping exclusively to the A1 domain. Aligning these sequences defined a minimal, overlapping segment spanning P1254-A1461, which encompasses the C1272-C1458 cystine loop. Analysis of phage carrying a mutated A1 segment (C1272/1458A) confirmed the requirement of the cystine loop for optimal binding. Four rounds of affinity maturation of a randomly mutagenized A1 phage library identified 10 and 14 unique mutants associated with enhanced platelet binding in the presence and absence of botrocetin, respectively, with 2 mutants (S1370G and I1372V) common to both conditions. These results demonstrate the utility of filamentous phage for studying VWF protein structure-function and identify a minimal, contiguous peptide that bind to formalin-fixed platelets, confirming the importance of the VWF A1 domain with no evidence for another independently platelet-binding segment within VWF. These findings also point to key structural elements within the A1 domain that regulate VWF-platelet adhesion.

Vhl deletion in osteoblasts boosts cellular glycolysis and improves global glucose metabolism

PubMed Central

Dirckx, Naomi; Tower, Robert J.; Mercken, Evi M.; Moreau-Triby, Caroline; Breugelmans, Tom; Nefyodova, Elena; Cardoen, Ruben; Mathieu, Chantal; Van der Schueren, Bart; Confavreux, Cyrille B.; Clemens, Thomas L.

2018-01-01

The skeleton has emerged as an important regulator of systemic glucose homeostasis, with osteocalcin and insulin representing prime mediators of the interplay between bone and energy metabolism. However, genetic evidence indicates that osteoblasts can influence global energy metabolism through additional, as yet unknown, mechanisms. Here, we report that constitutive or postnatally induced deletion of the hypoxia signaling pathway component von Hippel–Lindau (VHL) in skeletal osteolineage cells of mice led to high bone mass as well as hypoglycemia and increased glucose tolerance, not accounted for by osteocalcin or insulin. In vitro and in vivo data indicated that Vhl-deficient osteoblasts displayed massively increased glucose uptake and glycolysis associated with upregulated HIF-target gene expression, resembling the Warburg effect that typifies cancer cells. Overall, the glucose consumption by the skeleton was increased in the mutant mice, as revealed by 18F-FDG radioactive tracer experiments. Moreover, the glycemia levels correlated inversely with the level of skeletal glucose uptake, and pharmacological treatment with the glycolysis inhibitor dichloroacetate (DCA), which restored glucose metabolism in Vhl-deficient osteogenic cells in vitro, prevented the development of the systemic metabolic phenotype in the mutant mice. Altogether, these findings reveal a novel link between cellular glucose metabolism in osteoblasts and whole-body glucose homeostasis, controlled by local hypoxia signaling in the skeleton. PMID:29431735

Pregnancy and delivery in women with von Willebrand's disease and different von Willebrand factor mutations.

PubMed

Castaman, Giancarlo; Tosetto, Alberto; Rodeghiero, Francesco

2010-06-01

Pregnancy in von Willebrand's disease may carry a significant risk of bleeding. Information on changes in factor VIII and von Willebrand factor and pregnancy outcome in relation to von Willebrand factor gene mutations are very scanty. We examined biological response to desmopressin, changes in factor VIII and von Willebrand factor and pregnancy outcome in a cohort of 23 women with von Willebrand's disease characterized at molecular level and prospectively followed during 2000-2007. Thirty-one pregnancies occurred during the study period. Remarkably, similar changes of factor VIII and von Willebrand factor were observed after desmopressin and during pregnancy in nine women with R854Q, R1374H, V1665E, V1822G and C2362F mutations. Women with von Willebrand's disease and R1205H and C1130F mutations (17 pregnancies in 12 women) had only a slight increase of factor VIII and von Willebrand factor during pregnancy while their response to desmopressin was marked but short-lived. For these women, two to three desmopressin administrations within the first 48 hours were sufficient to successfully manage vaginal delivery. Two women with recessive von Willebrand's disease due to compound heterozygosity for different gene mutations had a spontaneous, major increase in factor VIII while von Willebrand factor remained severely reduced. Desmopressin increased factor VIII and was clinically useful in the first case, while a factor VIII/von Willebrand factor concentrate was required in the second patient not responsive to the compound. Factor VIII/von Willebrand factor concentrate was also required for two women with type 2 A von Willebrand's disease with V1665E mutations who had no von Willebrand factor activity change during pregnancy. In one of them, delayed bleeding occurred 15 days later requiring treatment with Factor VIII/von Willebrand factor concentrate. No miscarriages or stillbirths occurred. Close follow-up and detailed guidelines for the management of parturition have produced a very low rate of immediate and late bleeding complications in this setting. Desmopressin was effective and safe in preventing significant bleeding at delivery in most of these patients.

Gravity Effects in Diffusive Coarsening of Bubble Lattices: von Neumann's Law

NASA Technical Reports Server (NTRS)

Noever, David A.

2000-01-01

von Neumann modelled the evolution of two-dimensional soap froths as a purely diffusive phenomenon; the area growth of a given cell was found to depend only on the geometry of the bubble lattice. In the model, hexagons are stable, pentagons shrink and heptagons grow. The simplest equivalent to the area growth law is / approximately t(sub beta). The result depends on assuming (1) an incompressible gas; (2) bubble walls which meet at 120 deg and (3) constant wall thickness and curvature. Each assumption is borne out in experiments except the last one: bubble wall thickness between connecting cells varies in unit gravity because of gravity drainage. The bottom part of the soap membrane is thickened, the top part is thinned, such that gas diffusion across the membrane shows a complex dependence on gravity. As a result, experimental tests of von Neumann's law have been influenced by effects of gravity; fluid behavior along cell borders can give non-uniform wall thicknesses and thus alter the effective area and gas diffusion rates between adjacent bubbles. For area plotted as a function of time, Glazier (J.A. Glazier, S.P. Gross, and I. Stavans, Phys. Rev. A. 36, 306 (1987); J. Stavans, J.A, Glazier, Phys. Rev. Lett. 62, 1318 (1989).) suggest that in some cases their failure to observe von Neumann's predicted growth exponent ((sup beta)theor(sup =1; beta)exp(sup =0.70 + 0.10)) may have been the result of such "fluid drainage onto the lower glass plate". Additional experiments which varied plate spacing gave different beta exponents in a fashion consistent with this suggestion. During preliminary long duration experiments (approximately 100 h) aboard Spacelab-J, a low-gravity test of froth coarsening has examined (1) power law scaling of von Neumann's law (beta values) in the appropriate diffusive limits; (2) new bubble lattice dynamics such as greater fluid wetting behavior on froth membranes in low gravity; and (3) explicit relations for the gravity dependence of the second moment (or disorder parameter) governing the geometric spread in cell-sidedness around the mean of perfect hexagonal filling. By reducing the gravity-induced distortion in lattice wall thickness, the diffusion-limited regime of bubble coarsening becomes available for performing critical tests of network dynamics.

In vitro selection of resistance in haemophilus influenzae by 4 quinolones and 5 beta-lactams.

PubMed

Clark, Catherine; Kosowska, Klaudia; Bozdogan, Bülent; Credito, Kim; Dewasse, Bonifacio; McGhee, Pamela; Jacobs, Michael R; Appelbaum, Peter C

2004-05-01

We tested abilities of ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, amoxicillin, amoxicillin/clavulanate, cefixime, cefpodoxime, and cefdinir to select resistant mutants in 5 beta-lactamase positive and 5 beta-lactamase negative Haemophilus influenzae strains by single and multistep methodology. In multistep tests, amoxicillin, amoxicillin/clavulanate and cefpodoxime exposure did not cause >4-fold minimum inhibitory concentration (MIC) increase after 50 days. One mutant selected by cefdinir had one amino acid substitution (Gly490Glu) in PBP3 and became resistant to cefdinir. Cefixime exposure caused 8-fold MIC-increase in 1 strain with TEM but the mutant remained cefixime susceptible and had no alteration in PBP3 or TEM. Among 10 strains tested, ciprofloxacin, moxifloxacin, gatifloxacin, levofloxacin caused >4-fold MIC increase in 6, 6, 5, and 2 strain, respectively. Despite the increases in quinolone MICs, none of the mutants became resistant to quinolones by established criteria. Quinolone selected mutants had quindone resistance-determining region (QRDR) alterations in GyrA, GyrB, ParC, ParE. Four quinolone mutants had no QRDR alterations. Among beta-lactams cefdinir and cefixime selected one mutant each with higher MICs however amoxicillin, amoxicillin/clavulanate, and cefpodoxime exposure did not select resistant mutants.

Experimente ueber den Einflusse von Metaboliten und Antimetaboliten am Modell von Trichomonas Vaginalis. VIII. Mitteilung: Experiments mit Hormonen (Experiments on the Influence of Metabolites and Antimetabolites on the Model of Trichomonas Vaginalis. VIII. Communication: Experiments with Hormones),

DTIC Science & Technology

experiments were performed on 7 trichomonas vaginalis strains. The test cultures with serotonin, oestron, testosteron and methyltestosteron grew at...The present study has been concerned with the influence of some hormones upon trichomonas growth. The following substances were used for our...ml onward. Adrenalin and noradrenalin have generally inhibiting action (from 0.80 mg/ml onward) upon trichomonas growth. The antihormone 3.5-dijodtyrosin does rarely influence the growth of trichomonas . (Author)

8. Photocopied August 1978. BREAKING CONCRETE BARS, JULY 1898. TESTING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

8. Photocopied August 1978. BREAKING CONCRETE BARS, JULY 1898. TESTING MACHINE USED BY VON SCHON IN EXPERIMENTS ON METHODS OF MIXING CONCRETE AND ON CONCRETE AGGREGATES WHICH USED LOCAL MATERIALS. (4) - Michigan Lake Superior Power Company, Portage Street, Sault Ste. Marie, Chippewa County, MI

Diagnosis and management of von Willebrand's syndrome.

PubMed

Rick, M E

1994-05-01

von Willebrand's disease is the most common of the inherited bleeding disorders. It is caused by quantitative and/or qualitative abnormalities of von Willebrand factor, and it usually presents with bleeding from mucosal surfaces. The diagnosis is confirmed by measuring von Willebrand factor activity and antigen levels, factor VIII activity, and performing a multimer analysis of von Willebrand factor. Treatment may require plasma-derived concentrates, but can often be accomplished with DDAVP, a vasopressin analogue that causes transient release of von Willebrand factor from body storage sites.

Two distinct forms of Factor VIII coagulant protein in human plasma. Cleavage by thrombin, and differences in coagulant activity and association with von Willebrand factor.

PubMed Central

Weinstein, M J; Chute, L E

1984-01-01

We have characterized Factor VIII coagulant protein, present in normal human plasma, that reacts with a specific human 125I-labeled anti-human VIII:C antigen Fab antibody fragment. Two major Factor VIII coagulant antigen populations were present. The first, approximately 85% of the total antigen, was bound to von Willebrand factor and when tested in a standard one-stage assay had Factor VIII coagulant activity. The second antigenic population, eluting near fibrinogen when plasma was gel filtered, was not bound to von Willebrand protein, did not have Factor VIII coagulant activity unless activated, but did block anti-VIII:C Fab neutralization of clotting activity. The two antigenic populations were separable by cryoprecipitation and agarose gel electrophoresis. Although the two antigenic populations differed in their Factor VIII coagulant activity and in their binding to von Willebrand factor, the principal member of both populations is of mol wt 2.4 X 10(5). Both antigens, when proteolyzed by thrombin, were quickly converted to a 1 X 10(5)-mol wt form in association with the appearance of VIII:C activity. The 1 X 10(5)-mol wt antigen was further slowly degraded to an 8 X 10(4)-mol wt form while Factor VIII coagulant activity declined. These results demonstrate the presence of an inactive Factor VIII coagulant protein in plasma, not associated with von Willebrand factor, that can react with thrombin to yield Factor VIII coagulant activity. Images PMID:6421875

A note on derivations of Murray-von Neumann algebras.

PubMed

Kadison, Richard V; Liu, Zhe

2014-02-11

A Murray-von Neumann algebra is the algebra of operators affiliated with a finite von Neumann algebra. In this article, we first present a brief introduction to the theory of derivations of operator algebras from both the physical and mathematical points of view. We then describe our recent work on derivations of Murray-von Neumann algebras. We show that the "extended derivations" of a Murray-von Neumann algebra, those that map the associated finite von Neumann algebra into itself, are inner. In particular, we prove that the only derivation that maps a Murray-von Neumann algebra associated with a factor of type II1 into that factor is 0. Those results are extensions of Singer's seminal result answering a question of Kaplansky, as applied to von Neumann algebras: The algebra may be noncommutative and may even contain unbounded elements.

Early Rockets

NASA Image and Video Library

1950-01-01

Test firing of a Redstone Missile at Redstone Test Stand in the early 1950's. The Redstone was a high-accuracy, liquid-propelled, surface-to-surface missile developed by the von Braun Team under the management of the U.S. Army. The Redstone was the first major rocket development program in the United States.

Observed-Score Equating with a Heterogeneous Target Population

ERIC Educational Resources Information Center

Duong, Minh Q.; von Davier, Alina A.

2012-01-01

Test equating is a statistical procedure for adjusting for test form differences in difficulty in a standardized assessment. Equating results are supposed to hold for a specified target population (Kolen & Brennan, 2004; von Davier, Holland, & Thayer, 2004) and to be (relatively) independent of the subpopulations from the target population (see…

High-Throughput Parallel Sequencing to Measure Fitness of Leptospira interrogans Transposon Insertion Mutants during Acute Infection

PubMed Central

Matsunaga, James; Haake, David A.

2016-01-01

Pathogenic species of Leptospira are the causative agents of leptospirosis, a zoonotic disease that causes mortality and morbidity worldwide. The understanding of the virulence mechanisms of Leptospira spp is still at an early stage due to the limited number of genetic tools available for this microorganism. The development of random transposon mutagenesis in pathogenic strains a decade ago has contributed to the identification of several virulence factors. In this study, we used the transposon sequencing (Tn-Seq) technique, which combines transposon mutagenesis with massive parallel sequencing, to study the in vivo fitness of a pool of Leptospira interrogans mutants. We infected hamsters with a pool of 42 mutants (input pool), which included control mutants with insertions in four genes previously analyzed by virulence testing (loa22, ligB, flaA1, and lic20111) and 23 mutants with disrupted signal transduction genes. We quantified the mutants in different tissues (blood, kidney and liver) at 4 days post-challenge by high-throughput sequencing and compared the frequencies of mutants recovered from tissues to their frequencies in the input pool. Control mutants that were less fit in the Tn-Seq experiment were attenuated for virulence when tested separately in the hamster model of lethal leptospirosis. Control mutants with unaltered fitness were as virulent as the wild-type strain. We identified two mutants with the transposon inserted in the same putative adenylate/guanylate cyclase gene (lic12327) that had reduced in vivo fitness in blood, kidney and liver. Both lic12327 mutants were attenuated for virulence when tested individually in hamsters. Growth of the control mutants and lic12327 mutants in culture medium were similar to that of the wild-type strain. These results demonstrate the feasibility of screening large pools of L. interrogans transposon mutants for those with altered fitness, and potentially attenuated virulence, by transposon sequencing. PMID:27824878

Study of chromatic adaptation using memory color matches, Part II: colored illuminants.

PubMed

Smet, Kevin A G; Zhai, Qiyan; Luo, Ming R; Hanselaer, Peter

2017-04-03

In a previous paper, 12 corresponding color data sets were derived for 4 neutral illuminants using the long-term memory colours of five familiar objects. The data were used to test several linear (one-step and two-step von Kries, RLAB) and nonlinear (Hunt and Nayatani) chromatic adaptation transforms (CAT). This paper extends that study to a total of 156 corresponding color sets by including 9 more colored illuminants: 2 with low and 2 with high correlated color temperatures as well as 5 representing high chroma adaptive conditions. As in the previous study, a two-step von Kries transform whereby the degree of adaptation D is optimized to minimize the DEu'v' prediction errors outperformed all other tested models for both memory color and literature corresponding color sets, whereby prediction errors were lower for the memory color set. Most of the transforms tested, except the two- and one-step von Kries models with optimized D, showed large errors for corresponding color subsets that contained non-neutral adaptive conditions as all of them tended to overestimate the effective degree of adaptation in this study. An analysis of the impact of the sensor space primaries in which the adaptation is performed was found to have little impact compared to that of model choice. Finally, the effective degree of adaptation for the 13 illumination conditions (4 neutral + 9 colored) was successfully modelled using a bivariate Gaussian in a Macleod-Boyton like chromaticity diagram.

Biological diagnosis of von Willebrand disease: analytical characteristics of Innovance vWF:Ac assay kit on STA-R Evolution Expert series analyzer (Stago).

PubMed

Florin, Cécile; Garraud, Olivier; Molliex, Serge; Tardy, Brigitte; Campos, Lydia; Scherrer, Carine

2016-06-01

The Innovance VWF:Ac test (Siemens) has the particularity to assess the binding capacity of von Willebrand factor (VWF) to recombinant platelet GPIb mutated in the absence of ristocetin. Our study aimed to evaluate and validate according to standard NF EN ISO 15189 the original protocol adaptation on STA-R Evolution series analyser (Diagnostica Stago). We evaluated the performance in terms of imprecision and we validate additional parameters necessary in range B as recommended by the SH GTA 04 (Cofrac). We compared the new assay with the reference assay: ristocetin cofactor activity (VWF:RCo) performed on the BCS-XP analyser by testing retrospectively samples from 82 healthy normal subjects and 61 patients with von Willebrand disease (VWD). This new assay is consistent with objectives set in terms of imprecision with CV around 4%. Excepted limit of quantification higher, additional parameters evaluated in range B have been validated. The Innovance VWF: Ac assay allowed the detection of all deficits of VWF already detected by the VWF:RCo test on the BCS-XP. This adjustment on STA-R analyser therefore has satisfactory analytical performance criteria. Apart from the limit of quantification, this reagent can be used according to the recommendations specified in the original protocol adaptation. Its performance and compatibility with the spot measurement allow the diagnosis and therapeutic monitoring of VWD according to current requirements and guidelines.

Synesthesia and memory: color congruency, von Restorff, and false memory effects.

PubMed

Radvansky, Gabriel A; Gibson, Bradley S; McNerney, M Windy

2011-01-01

In the current study, we explored the influence of synesthesia on memory for word lists. We tested 10 grapheme-color synesthetes who reported an experience of color when reading letters or words. We replicated a previous finding that memory is compromised when synesthetic color is incongruent with perceptual color. Beyond this, we found that, although their memory for word lists was superior overall, synesthetes did not exhibit typical color- or semantic-defined von Restorff isolation effects (von Restorff, 1933) compared with control participants. Moreover, our synesthetes exhibited a reduced Deese-Roediger-McDermott false memory effect (Deese, 1959; Roediger & McDermott, 1995). Taken as a whole, these findings are consistent with the idea that color-grapheme synesthesia can lead people to place a greater emphasis on item-specific processing and surface form characteristics of words in a list (e.g., the letters that make them up) relative to relational processing and more meaning-based processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

A note on derivations of Murray–von Neumann algebras

PubMed Central

Kadison, Richard V.; Liu, Zhe

2014-01-01

A Murray–von Neumann algebra is the algebra of operators affiliated with a finite von Neumann algebra. In this article, we first present a brief introduction to the theory of derivations of operator algebras from both the physical and mathematical points of view. We then describe our recent work on derivations of Murray–von Neumann algebras. We show that the “extended derivations” of a Murray–von Neumann algebra, those that map the associated finite von Neumann algebra into itself, are inner. In particular, we prove that the only derivation that maps a Murray–von Neumann algebra associated with a factor of type II1 into that factor is 0. Those results are extensions of Singer’s seminal result answering a question of Kaplansky, as applied to von Neumann algebras: The algebra may be noncommutative and may even contain unbounded elements. PMID:24469831

Neurobehavioral Mutants Identified in an ENU Mutagenesis Project

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cook, Melloni N.; Dunning, Jonathan P; Wiley, Ronald G

2007-01-01

We report on a behavioral screening test battery that successfully identified several neurobehavioral mutants among a large-scale ENU-mutagenized mouse population. Large numbers of ENU mutagenized mice were screened for abnormalities in central nervous system function based on abnormal performance in a series of behavior tasks. We developed and employed a high-throughput screen of behavioral tasks to detect behavioral outliers. Twelve mutant pedigrees, representing a broad range of behavioral phenotypes, have been identified. Specifically, we have identified two open field mutants (one displaying hyper-locomotion, the other hypo-locomotion), four tail suspension mutants (all displaying increased immobility), one nociception mutant (displaying abnormal responsivenessmore » to thermal pain), two prepulse inhibition mutants (displaying poor inhibition of the startle response), one anxiety-related mutant (displaying decreased anxiety in the light/dark test), and one learning and memory mutant (displaying reduced response to the conditioned stimulus) These findings highlight the utility of a set of behavioral tasks used in a high throughput screen to identify neurobehavioral mutants. Further analysis (i.e., behavioral and genetic mapping studies) of mutants is in progress with the ultimate goal of identification of novel genes and mouse models relevant to human disorders as well as the identification of novel therapeutic targets.« less

Mice That Lack Thrombospondin 2 Display Connective Tissue Abnormalities That Are Associated with Disordered Collagen Fibrillogenesis, an Increased Vascular Density, and a Bleeding Diathesis

PubMed Central

Kyriakides, Themis R.; Zhu, Yu-Hong; Smith, Lynne T.; Bain, Steven D.; Yang, Zhantao; Lin, Ming T.; Danielson, Keith G.; Iozzo, Renato V.; LaMarca, Mary; McKinney, Cindy E.; Ginns, Edward I.; Bornstein, Paul

1998-01-01

Thrombospondin (TSP) 2, and its close relative TSP1, are extracellular proteins whose functions are complex, poorly understood, and controversial. In an attempt to determine the function of TSP2, we disrupted the Thbs2 gene by homologous recombination in embryonic stem cells, and generated TSP2-null mice by blastocyst injection and appropriate breeding of mutant animals. Thbs2−/− mice were produced with the expected Mendelian frequency, appeared overtly normal, and were fertile. However, on closer examination, these mice displayed a wide variety of abnormalities. Collagen fiber patterns in skin were disordered, and abnormally large fibrils with irregular contours were observed by electron microscopy in both skin and tendon. As a functional correlate of these findings, the skin was fragile and had reduced tensile strength, and the tail was unusually flexible. Mutant skin fibroblasts were defective in attachment to a substratum. An increase in total density and in cortical thickness of long bones was documented by histology and quantitative computer tomography. Mutant mice also manifested an abnormal bleeding time, and histologic surveys of mouse tissues, stained with an antibody to von Willebrand factor, showed a significant increase in blood vessels. The basis for the unusual phenotype of the TSP2-null mouse could derive from the structural role that TSP2 might play in collagen fibrillogenesis in skin and tendon. However, it seems likely that some of the diverse manifestations of this genetic disorder result from the ability of TSP2 to modulate the cell surface properties of mesenchymal cells, and thus, to affect cell functions such as adhesion and migration. PMID:9442117

Impact of early developmental fluoride exposure on the peripheral pain sensitivity in mice.

PubMed

Ma, Jing; Liu, Fei; Liu, Peng; Dong, Ying-Ying; Chu, Zheng; Hou, Tie-Zhou; Dang, Yong-Hui

2015-12-01

Consumption of high concentration of fluoride in the drinking water would cause the fluorosis and chronic pain. Similar pain syndrome appeared in the patients in fluoride therapy of osteoporotic. The aim of the current study was to examine whether exposing immature mice to fluoride would modify the peripheral pain sensitivity or even cause a pain syndrome. We gave developmental fluoride exposure to mice in different concentration (0mg/L, 50mg/L and 100mg/L) and evaluated their basal pain threshold. Von Frey hair test, hot plate test and formalin test were conducted to examine the mechanical, thermal nociceptive threshold and inflammatory pain, respectively. In addition, the expression of hippocampal brain-derived neurotrophic factor (BDNF) was also evaluated by Western blotting. Hyperalgesia in fluoride exposure mice was exhibited in the Von Frey hair test, hot plate test and formalin test. Meanwhile, the expression of BDNF was significantly higher than that of control group. The results suggest that early developmental fluoride exposure may lower the basal pain threshold and be associated with the increasing of BDNF expression in hippocampus. Copyright © 2015 Elsevier Ltd. All rights reserved.

Metastatic phaeochromocytoma in a 23-year-old woman with an unclassified variant in the von Hippel Lindau disease gene: how can the pathogenicity of this variant be determined?

PubMed

Russell, Nicholas; Delatycki, Martin; Grossmann, Mathis

2015-07-01

A 23-year-old woman with metastatic phaeochromocytoma was found to have a previously unclassified variant in the von Hippel Lindau disease gene (c.361G>C). We use this case to highlight the issue of unclassified single nucleotide variants and the approaches to help predict whether they are disease causing or neutral. With increasing use of genetic testing, and widespread clinical use of next-generation sequencing around the corner, this issue is likely to become more prominent. © 2015 John Wiley & Sons Ltd.

phoP, SPI1, SPI2 and aroA mutants of Salmonella Enteritidis induce a different immune response in chickens.

PubMed

Elsheimer-Matulova, Marta; Varmuzova, Karolina; Kyrova, Kamila; Havlickova, Hana; Sisak, Frantisek; Rahman, Masudur; Rychlik, Ivan

2015-09-17

Poultry is the most frequent reservoir of non-typhoid Salmonella enterica for humans. Understanding the interactions between chickens and S. enterica is therefore important for vaccine design and subsequent decrease in the incidence of human salmonellosis. In this study we therefore characterized the interactions between chickens and phoP, aroA, SPI1 and SPI2 mutants of S. Enteritidis. First we tested the response of HD11 chicken macrophage-like cell line to S. Enteritidis infection monitoring the transcription of 36 genes related to immune response. All the mutants and the wild type strain induced inflammatory signaling in the HD11 cell line though the response to SPI1 mutant infection was different from the rest of the mutants. When newly hatched chickens were inoculated, the phoP as well as the SPI1 mutant did not induce an expression of any of the tested genes in the cecum. Despite this, such chickens were protected against challenge with wild-type S. Enteritidis. On the other hand, inoculation of chickens with the aroA or SPI2 mutant induced expression of 27 and 18 genes, respectively, including genes encoding immunoglobulins. Challenge of chickens inoculated with these two mutants resulted in repeated induction of 11 and 13 tested genes, respectively, including the genes encoding immunoglobulins. In conclusion, SPI1 and phoP mutants induced protective immunity without inducing an inflammatory response and antibody production. Inoculation of chickens with the SPI2 and aroA mutants also led to protective immunity but was associated with inflammation and antibody production. The differences in interaction between the mutants and chicken host can be used for a more detailed understanding of the chicken immune system.

FORS am Very Large Telescope der Europäischen Südsternwarte

NASA Astrophysics Data System (ADS)

1998-09-01

Erstes wissenschaftliches Beobachtungsinstrument liefert eindrucksvolle Bilder Entsprechend dem straffen Zeitplan wird das ESO Very Large Teleskop Projekt (VLT-Projekt) auf dem Cerro Paranal in Nord-Chile verwirklicht: die volle Betriebsbereitschaft des ersten der vier 8,2m-Einzelteleskope wird Anfang des nächsten Jahres erreicht sein. Am 15. September 1998 wurde ein weiterer wichtiger Meilenstein erfolgreich, rechtzeitig und innerhalb des Kostenplans erreicht. Nur wenige Tage nach seiner Montage am ersten 8,2m-Einzelteleskop des VLT (UT1) konnte FORS1 ( FO cal R educer and S pectrograph) als erstes einer Gruppe leistungsfähiger und komplexer wissenschaftlicher Instrumente seine Beobachtungstätigkeit beginnen. Von Anfang an konnte es eine Reihe exzellenter astronomischer Bilder aufnehmen. Dieses bedeutende Ereignis eröffnet eine Fülle neuer Möglichkeiten für die europäische Astronomie. FORS - ein Höhepunkt an Komplexität FORS1 und das zukünftige Zwillingsinstrument (FORS2) sind das Ergebnis einer der eingehendsten und fortschrittlichsten technologischen Studien, die je für ein Instrument der bodengebundenen Astronomie durchgeführt wurden. Dieses einzigartige Instrument ist nun im Cassegrain-Fokus installiert und verschwindet beinahe, trotz seiner Dimensionen von 3 x 1.5m (Gewicht 2.3t), unterhalb des riesigen 53 m 2 großen Zerodurspiegels. Um die große Spiegelfläche und die hervorragende Bildqualität von UT1 optimal auszunützen, wurde FORS speziell so konstruiert, daß es die lichtschwächsten und entferntesten Objekte im Weltall untersuchen kann. Bald wird dieses komplexe VLT-Instrument den europäischen Astronomen erlauben, die derzeitigen Beobachtungshorizonte entscheidend zu erweitern. Die beiden FORS-Instrumente sind Vielzweck-Beobachtungsinstrumente, die in mehreren unterschiedlichen Beobachtungsarten eingesetzt werden können. Beispielsweise können Bilder mit zwei verschiedenen Abbildungsmaßstäben (Vergrößerungen) sowie Spektren mit unterschiedlicher spektraler Auflösung von einzelnen oder mehreren Objekten aufgenommen werden. Dabei erlaubt der schnelle Wechsel zwischen den unterschiedlichen Beobachtungsarten z.B. zunächst die Aufnahme und direkt anschließend die Spektroskopie weit entfernter Galaxien. Damit kann dann u.a. die stellare Zusammensetzung und die Entfernung bestimmt werden. Als eines der leistungsfähigsten astronomischen Instrumente seiner Art wird FORS1 ein wahres Arbeitspferd für die Untersuchung des fernen Universums darstellen. Der Bau von FORS Das FORS-Projekt wird unter ESO-Kontrakt von einem Konsortium dreier deutscher astronomischer Institute durchgeführt, der Landessternwarte Heidelberg und den Universitäts-Sternwarten von Göttingen and München. Bis zur Beendigung des Projekts werden die beteiligten Institute Arbeit im Umfang von ca. 180 Mann-Jahren eingebracht haben. Bei der Landessternwarte Heidelberg lag die Leitung des Projekts. Hier wurde außerdem das gesamte optische System konstruiert, die Beschaffung der Komponenten der abbildenden Optik und der Zusatzoptiken für Spektroskopie und Polarimetrie durchgeführt und die spezielle Computersoftware geschrieben, mit der die von FORS gelieferten Daten verarbeitet und ausgewertet werden. Darüber hinaus wurde in der Werkstatt der Sternwarte ein Teleskopsimulator gebaut, mit dem alle wesentlichen Funktionen von FORS in Europa getestet werden konnten, bevor das Instrument zum Paranal (Chile) transportiert wurde. An der Universitäts-Sternwarte Göttingen wurden Konstruktion, Herstellung und Zusammenbau der gesamten Mechanik von FORS durchgeführt. Der größte Teil der Präzisionsteile, insbesondere der Multispalteinheit, wurde in der feinmechanischen Werkstatt der Sternwarte hergestellt. Die Beschaffung der großen Instrumentengehäuse und Flansche, die Computeranalysen für mechanische und thermische Stabilität des empfindlichen Spektrographen und die Herstellung der speziellen Werkzeuge für Handhabung, Wartung und Justierung lag ebenso in der Verantwortung dieser Sternwarte wie die Tests der zahlreichen opto- und elektromechanischen Funktionen. Die Universitäts-Sternwarte München war verantwortlich für das Projektmanagement, Integration und Test des gesamten Instruments im Labor, für Planung und Einbau aller Elektronik und Elektromechanik, sowie für Entwicklung und Test der gesamten Software, die FORS in allen Teilen vollständig per Computer steuert (z.B. Filter- und Grismräder, Verschlüsse, Spalteinheit für die Vielspaltspektroskopie, Masken, alle optischen Komponenten, Elektromotoren, Encoder usw.). Zusätzlich wurde Computersoftware geschrieben, mit der die komplexen astronomischen Beobachtungen mit FORS vorbereitet werden und das Verhalten des Instruments durch eine ständige Kontrolle der gesammelten wissenschaftlichen Daten überwacht wird. Als Gegenleistung für den Bau von FORS erhalten die Astronomen der drei beteiligten Institute des FORS-Konsortiums eine gewisse Anzahl von Nächten an "garantierter Beobachtungszeit" am VLT. In dieser Beobachtungszeit werden verschiedene Forschungsprojekte durchgeführt, deren Themen unter anderem von kleinen Körpern im äußeren Sonnensystem über Untersuchungen von Sternen im Endstadium und den von ihnen abgestoßenen Gaswolken bis zur Erforschung ferner Galaxien und Quasare reichen, die Aufschluß über die frühen Zeiten unseres Universums geben. Erste Tests von FORS1 am VLT-UT1: ein großartiger Erfolg Nach sorgfältiger Vorbereitung hat das FORS-Konsortium nun mit der Inbetriebnahme ("Commissioning") des Instruments begonnen. Dazu gehören ein eingehender Nachweis der spezifizierten Leistungsfähigkeit am Teleskop, die Überprüfung der korrekten Funktionsweise unter Softwaresteuerung vom Kontrollraum auf Paranal, und am Ende dieses Prozesses eine Demonstration, daß das Instrument seinen angestrebten wissenschaftlichen Zweck erfüllt. Während der Durchführung dieser Tests gelangen dem Commissioning-Team auf Paranal eine Reihe von Aufnahmen verschiedener astronomischer Objekte, von denen einige hier wiedergegeben sind. Sie wurden alle mit FORS in der Standardauflösung gewonnen (Bildfeldgröße 6.8 x 6.8 Bogenminuten, Pixelgröße 0.20 Bogensekunden) und zeigen einige der eindrucksvollen Möglichkeiten, die das neue Instrument bietet. Spiralgalaxie NGC 1288 ESO PR Photo 37a/98 ESO PR Photo 37a/98 [Preview - JPEG: 800 x 908 pix - 224k] [High-Res - JPEG: 3000 x 3406 pix - 1.5Mb] Farbaufnahme der Spiralgalaxie NGC 1288, aufgenommen in der ersten Beobachtungsnacht von FORS ("Nacht des ersten Lichts"). Das erste Photo zeigt eine Dreifarbenaufnahme der schönen Spiralgalaxie NGC 1288 im südlichen Sternbild Fornax. PR Photo 37a/98 umfaßt das gesamte Feld, das mit der 2048 x 2048 Pixel großen CCD-Kamera abgebildet wurde. Es wurde aus drei CCD-Aufnahmen zusammengesetzt, die bei gutem Seeing in verschiedenen Farben in der "Nacht des ersten Lichts" (15. September 1998) aufgenommen wurden. Diese Galaxie mit einem Durchmesser von rund 200000 Lichtjahren ist etwa 300 Millionen Lichtjahre entfernt, ihre Fluchtgeschwindigkeit beträgt 4500 km/sec. Technische Informationen : Photo 37a/98 ist ein Komposit von drei Aufnahmen in den drei Filtern B (420nm, 6 Minuten belichtet), V (530nm, 3 Minuten) und I (800nm, 3 Minuten) während einer Periode mit 0.7 Bogensekunden Seeing. Das gezeigte Feld ist 6.8 x 6.8 Bogenminuten groß. Norden ist links, Osten unten. Entfernter Galaxienhaufen ESO PR Photo 37b/98 ESO PR Photo 37b/98 [Preview - JPEG: 657 x 800 pix - 248k] [High-Res - JPEG: 2465 x 3000 pix - 1.9Mb] Ein ungewöhnlicher Galaxienhaufen in der Umgebung des Quasars PB5763 . ESO PR Photo 37c/98 ESO PR Photo 37c/98 [Preview - JPEG: 670 x 800 pix - 272k] [High-Res - JPEG: 2512 x 3000 pix - 1.9Mb] Vergrößerung von PR Photo 37b/98; sie zeigt mehr Einzelheiten des ungewöhnlichen Galaxienhaufens. Die nächsten Photos wurden von einer 5-minütigen Aufnahme im Nahen Infrarot reproduziert, die ebenfalls in der "Nacht des ersten Lichts" von FORS1 (15. September 1998) gewonnen wurde. PR Photo 37b/98 zeigt einen Himmelsausschnitt in der Nähe des Quasars PB5763, in dem auch ein ungewöhnlicher, sehr weit entfernter Haufen von Galaxien zu sehen ist. Er besteht aus einer großen Zahl lichtschwacher Galaxien, die bisher noch nicht eingehend untersucht wurden. Dieser Haufen ist ein gutes Beispiel für die Art von Objekten, auf die viel Beobachtungszeit mit FORS verwendet werden wird, sobald der reguläre Beobachtungsbetrieb begonnen hat. Eine Vergrößerung des gleichen Feldes ist in PR Photo 37c/98 wiedergegeben. Sie zeigt die einzelnen Mitglieder dieses Galaxienhaufens im Detail. Man beachte besonders die interessante spindelförmige Galaxie, die anscheinend einen äquatorialen Ring aufweist. Neben einer schönen Spiralgalaxie sind auch noch viele weitere lichtschwache Galaxien zu erkennen. Sie sind entweder Zwerggalaxien und Mitglieder des Haufens oder befinden sich sehr viel weiter entfernt im Hintergrund des Haufens. Technische Informationen : PR Photos 37b/98 (als Negativ reproduziert) und 37c/98 (Positiv) stammen von einer Aufnahme, die bei 0.8 Bogensekunden Seeing durch ein I-Filter (nahes Infrarot, 800nm) gewonnen wurde. Die Belichtungszeit betrug 5 Minuten, und es wurde eine Flatfield-Korrektur durchgeführt. Das gezeigte Feld ist 6.8 x 6.8 Bogenminuten bzw. 2.5 x 2.3 Bogenminuten groß. Norden ist links oben, Osten links unten. Spiralgalaxie NGC 1232 ESO PR Photo 37d/98 ESO PR Photo 37d/98 [Preview - JPEG: 800 x 912 pix - 760k] [High-Res - JPEG: 3000 x 3420 pix - 5.7Mb] Ein Farbbild der Spiralgalaxie NGC 1232, aufgenommen am 21. September 1998. ESO PR Photo 37e/98 ESO PR Photo 37e/98 [Preview - JPEG: 800 x 961 pix - 480k] [High-Res - JPEG: 3000 x 3602 pix - 3.5Mb] Vergrößerung des Zentrums von PR Photo 37d/98. Dieses spektakuläre Bild der großen Spiralgalaxie NGC 1232 (Photo 37d/98) wurde am 21. September 1998 unter guten Beobachtungsbedingungen erhalten. Es wurde aus drei Einzelaufnahmen im ultravioletten, blauen und roten Licht zusammengesetzt. Die Farben der verschiedenen Regionen sind deutlich sichtbar: Das Zentralgebiet enthält ältere, rötlich leuchtende Sterne (Photo 37e/98), während die Spiralarme von jungen, bläulichen Sternen und roten Sternentstehungsgebieten bevölkert sind. Man beachte die gestörte Begleitgalaxie am linken Rand (Photo 37d/98), die wie der griechische Buchstabe "Theta" aussieht. NGC 1232 liegt 20 Grad südlich des Himmelsäquators im Sternbild Eridanus. Obwohl die Entfernung dieser Galaxie ungefähr 100 Millionen Lichtjahre beträgt, kann man auf Grund der exzellenten Bildqualität einen unglaublichen Reichtum an Details erkennen. Bei dieser Entfernung entspricht die Kantenlänge des Bildfeldes etwa 200000 Lichtjahren oder etwa der doppelten Größe unserer Milchstraße. Technische Informationen : Photos 37d/98 und 37e/98 sind ein Komposit von drei Aufnahmen in den drei Filtern U (360nm, 10 Minuten belichtet), B (420nm, 6 Minuten) und R (600nm, 2 Minuten 30 Sekunden) während einer Periode mit 0.7 Bogensekunden Seeing. Das gezeigte Feld ist 6.8 x 6.8 Bogenminuten bzw. 1.6 x 1.8 Bogenminuten groß. Norden ist oben, Osten links. Note: [1] Diese Pressemitteilung wird gemeinsam (auf Englisch und Deutsch) von der Europäischen Südsternwarte, der Landessternwarte Heidelberg und den Universitäts-Sternwarten Göttingen und München herausgegeben. An English Version of this Press Release is also available. Zugang zu ESO Presseinformationen ESO Presseinformationen werden im World Wide Web zur Verfügung gestellt (URL: http://www.eso.org/outreach/press-rel/). ESO Pressephotos dürfen veröffentlicht werden, wenn die Europäische Südsternwarte als Urheber genannt wird.

[Kombinierte Anwendung von Strahlentherapie und adjuvanter Therapie mit einem Mistelextrakt (Viscum album L.) zur Behandlung des oralen malignen Melanoms beim Hund: Eine retrospektive Studie].

PubMed

von Bodungen, Uta; Ruess, Katja; Reif, Marcus; Biegel, Ulrike

2017-01-01

Hintergrund: Orale maligne Melanome (OMM) des Hundes zeichnen sich durch schnelles Wachstum, lokale Invasion und hohe Metastasierungsraten aus. Extrakte auf Basis von Viscum album L. (VAE) werden zunehmend in der Krebstherapie sowohl in der Human- als auch in der Veterinärmedizin eingesetzt. Ziel unserer Studie war es zu untersuchen, inwieweit die adjuvante Therapie mit VAE eine therapeutische Option zur Behandlung von OMM ist. Besonderes Augenmerk galt dabei der Überlebenszeit und möglichen Nebenwirkungen. Tiere und Methoden: 26 Hunde mit OMM, die in einem der größten veterinäronkologischen Zentren der Schweiz allesamt eine Strahlentherapie erhielten (teilweise nach operativer Tumorresektion) wurden in die retrospektive Studie eingeschlossen: 18 Hunde wurden mit VAE behandelt (1 ml VAE (Iscador®) in ansteigenden Konzentrationen von 0,1 bis 20 mg/ml subkutan 3-mal pro Woche (VAE-Gruppe), 8 erhielten keine adjuvante Behandlung (Vergleichsgruppe). Wir verglichen die Größenentwicklung der OMM sowie die Überlebenszeit. Ergebnisse: Patienten mit Bestrahlung und adjuvanter VAE-Therapie zeigten mit 236 Tagen eine signifikant längere mediane Überlebenszeit im Vergleich zu Patienten mit Bestrahlung, aber ohne adjuvante VAE-Therapie (49 Tage; Log-Rank-Test: p = 0,0047). Die VAE-Therapie verlängerte die Überlebenszeit um mehr als zwei Drittel (Hazard Ratio (HR) = 0,30, 95%-Konfidenzintervall (KI) 0,11-0,86; p = 0,024), während ein höheres Tumorstadium gemäß UICC (Union internationale contre le cancer) einen statistischen Trend zur Verdopplung des Sterberisikos zeigte (UICC-Stadium III/IV vs. I/II: HR = 2,12, 95%-KI 0,88-5,12; p = 0,095). Zwei Patienten zeigten milde Nebenwirkungen während der VAE-Behandlung. Einer der beiden zeigte 1 Tag lang ein selbstlimitiertes Fieber, bei dem anderen Patienten reduzierten wir die Dosis von einem konzentrierteren zu einem weniger konzentrierten VAE (Serie 0) aufgrund von Müdigkeit, die daraufhin verschwand. Schlussfolgerungen: VAE ist eine sichere, nebenwirkungsarme Behandlung und scheint sich positiv auf die Überlebenszeit von Hunden mit OMM auszuwirken. Somit ist dieser therapeutische Ansatz es wert, vermehrt bei der adjuvant zur Strahlentherapie eingesetzten Behandlung des OMM in Betracht gezogen zu werden. Die verglichenen Gruppen waren jedoch klein, divers und nicht konsistent hinsichtlich aller prognostischen Parameter. Eine prospektive Studie mit einer größeren Studienpopulation wäre daher von Interesse. © 2017 S. Karger GmbH, Freiburg.

Laboratory diagnosis of von Willebrand disease type 1/2E (2A subtype IIE), type 1 Vicenza and mild type 1 caused by mutations in the D3, D4, B1-B3 and C1-C2 domains of the von Willebrand factor gene. Role of von Willebrand factor multimers and the von Willebrand factor propeptide/antigen ratio.

PubMed

Gadisseur, Alain; Berneman, Zwi; Schroyens, Wilfried; Michiels, Jan Jacques

2009-01-01

Autosomal dominant von Willebrand disease (VWD) type 1/2E is a quantitative/qualitative defect in the von Willebrand factor (VWF) caused by heterozygous cysteine and non-cysteine mutations in the D3 domain of the VWF gene and results in a secretion-multimerization-clearance defect in mutant VWF with the loss of large VWF multimers not due to proteolysis. The multimers of patients with dominant VWD type 1/2E due to mutations in the D3 domain show an aberrant triplet structure with lack of outer bands but with pronounced inner bands of the triplet structure combined with a relative decrease in large multimers reflecting heterozygosity for multimerization defects. There is a good response to desmopressin (DDAVP) followed by rapid clearance of VWF:antigen (Ag), factor VIII coagulant activity (FVIII:C) and VWF:ristocetin cofactor activity (RCo) as the main cause of VWD type 1 or 2 with typical 2E multimeric pattern (VWD type 1/2E). Cysteine mutations in the D3 domains (C1130, C1149 and C1190) show pronounced features of VWD 1/2E with the relative loss of large and relative increase in small VWF multimers with abnormal triplet structure in heterozygotes. Such abnormalities are less pronounced in patients with a milder form of VWD type 1 due to non-cysteine mutations W1144G, T1156M and W1120S in the D3 domain. VWD type 1 Vicenza is caused by the R1205H mutation in the D3 domain and characterized by equally low levels of FVIII:C, VWF:Ag and VWF:RCo. The response to DDAVP in VWD Vicenza is good for FVIII:C, VWF:Ag and VWF:RCo, which is followed by a rapid clearance in less than a few hours of FVIII:C and VWF parameters. The ratios for FVIII:C/VWF:Ag, VWF:RCo/Ag and VWF:CB/Ag remain normal before and after DDAVP indicating that VWD Vicenza clearly differs from VWD type 1, 1/2E and 2M. A new set of missense mutations in D4, B1-B3 and C1-C2 domains has been discovered as the cause of a mild VWD type 1 secretion defect with normal VWF multimers or smeary VWF multimeric pattern. Cysteine mutations in exons 38, 40, 42 and 43 (D4, B1-B3 and C1 domain), show smeary patterns (either smf or sm), with the presence of large VWF multimers and a laboratory phenotype of mild VWD type 1 with variable penetrance of bleeding manifestations. Recent studies showed that the ratio of VWF propeptide (pp) to VWF:Ag can be used to predict a shorter than normal half-life for VWF:Ag. There is a strong inverse correlation between rapid clearance of VWF:Ag after DDAVP and increased VWFpp/Ag ratios >10 in VWD type 1 Vicenza, and >2 in VWD type 1/2E but normal or slightly increased (1-<2) VWFpp/Ag ratios in mild-type VWD due to nonsense or missense mutations in the D1, D2, D4, B and C domains. Copyright (c) 2009 S. Karger AG, Basel.

Invasive forstliche schad-organismen in Nordamerika

Treesearch

Christopher J. Fettig; Horst E.  Delb

2017-01-01

In Nordamerika sind Wälder infolge von Einwandernden, internationalem Handel und Tourismus traditionell stark von Einschleppungen gebietsfremder invasiver Schadorganismen betroffen. Infolge von Globalisierung und Klimawandel gibt es aufgrund der Ähnlichkeiten von Klima, Flora und Fauna zwischen Europa und Nordamerika viele Parallelen.

Verbesserung der Symmetrie von Hirnaufnahmen entlang der Sagittalebene

NASA Astrophysics Data System (ADS)

Ens, Konstantin; Wenzel, Fabian; Fischer, Bernd

Die lokale Symmetrie von Hirnscans entlang der Sagittalebene zu ermitteln und zu modizifieren, ist für eine Reihe neurologischer Anwendungen interessant. Beispielsweise kann der voxelweise Vergleich von rechter und linker Hirnhälfte nur dann Aufschluss über die Lokalisierung von Läsionen geben, wenn durch Transformation ein Hirnscan eine möglichst hohe Symmetrie aufweist. Ein weiteres Anwendungsgebiet ist die Visualisierung von medialen Hirnschnitten, für die die Trennfläche beider Hirnhälfte möglichst eben sein sollte. Diese Arbeit stellt die Entwicklung eines Verfahrens vor, mit dessen Hilfe die Symmetrie von Hirnaufnahmen entlang der Sagittalebene verbessert werden kann. Dies geschieht unter Verwendung von aktiven Konturen, die mit Hilfe einer neuartigen Kostenfunktion gesteuert werden. Experimente am Ende der Arbeit mit strukturellen Kernspinaufnahmen demonstrieren die Leistungsfähigkeit des Verfahrens.

Book Review: John von Neumann and the foundations of quantum physics. (Vienna Circle Institute yearbook (2000), 8) Miklos Redei and Michael Stoltzner (Eds.); Kluwer Academic Publishers, Dordrecht, 2001, pp., US 125, ISBN 0792368126

NASA Astrophysics Data System (ADS)

Lupher, Tracy

2003-12-01

Some people may be surprised to learn that John von Neumann's work on the foundations of quantum physics went far beyond what is contained within the pages of his Mathematical Foundations of Quantum Mechanics (MFQM) (von Neumann, 1955). However, this narrow focus often ignores von Neumann's later work on quantum logic and what are now called in his honor, von Neumann algebras. This volume honoring von Neumann's contributions to physics is unique in that, while it contains 12 papers that examine various aspects of von Neumann's work, it also contains two of his previously unpublished papers and some of his previously unpublished correspondence.

Evaluation of CLSI M44-A2 Disk Diffusion and Associated Breakpoint Testing of Caspofungin and Micafungin Using a Well-Characterized Panel of Wild-Type and fks Hot Spot Mutant Candida Isolates▿

PubMed Central

Arendrup, Maiken Cavling; Park, Steven; Brown, Steven; Pfaller, Michael; Perlin, David S.

2011-01-01

Disk diffusion testing has recently been standardized by the CLSI, and susceptibility breakpoints have been established for several antifungal compounds. For caspofungin, 5-μg disks are approved, and for micafungin, 10-μg disks are under evaluation. We evaluated the performances of caspofungin and micafungin disk testing using a panel of Candida isolates with and without known FKS echinocandin resistance mechanisms. Disk diffusion and microdilution assays were performed strictly according to CLSI documents M44-A2 and M27-A3. Eighty-nine clinical Candida isolates were included: Candida albicans (20 isolates/10 mutants), C. glabrata (19 isolates/10 mutants), C. dubliniensis (2 isolates/1 mutant), C. krusei (16 isolates/3 mutants), C. parapsilosis (14 isolates/0 mutants), and C. tropicalis (18 isolates/4 mutants). Quality control strains were C. parapsilosis ATCC 22019 and C. krusei ATCC 6258. The correlations between zone diameters and MIC results were good for both compounds, with identical susceptibility classifications for 93.3% of the isolates by applying the current CLSI breakpoints. However, the numbers of fks hot spot mutant isolates misclassified as being susceptible (S) (very major errors [VMEs]) were high (61% for caspofungin [S, ≥11 mm] and 93% for micafungin [S, ≥14 mm]). Changing the disk diffusion breakpoint to S at ≥22 mm significantly improved the discrimination. For caspofungin, 1 VME was detected (a C. tropicalis isolate with an F76S substitution) (3.5%), and for micafungin, 10 VMEs were detected, the majority of which were for C. glabrata (8/10). The broadest separation between zone diameter ranges for wild-type (WT) and mutant isolates was seen for caspofungin (6 to 12 mm versus −4 to 7 mm). In conclusion, caspofungin disk diffusion testing with a modified breakpoint led to excellent separation between WT and mutant isolates for all Candida species. PMID:21357293

TRPM3 and miR-204 establish a regulatory circuit that controls oncogenic autophagy in clear cell renal cell carcinoma

PubMed Central

Hall, Daniel P.; Cost, Nicholas G.; Hegde, Shailaja; Kellner, Emily; Mikhaylova, Olga; Stratton, Yiwen; Ehmer, Birgit; Abplanalp, William A.; Pandey, Raghav; Biesiada, Jacek; Harteneck, Christian; Plas, David R.; Meller, Jarek; Czyzyk-Krzeska, Maria F.

2014-01-01

Summary Autophagy promotes tumor growth by generating nutrients from the degradation of intracellular structures. Here we establish, using shRNAs, a dominant negative mutant, and a pharmacologic inhibitor, mefenamic acid (MFA), that the Transient Receptor Potential Melastatin 3 (TRPM3) channel promotes growth of clear cell renal cell carcinoma (ccRCC) and stimulates MAP1LC3A (LC3A) and MAP1LC3B (LC3B) autophagy. Increased expression of TRPM3 in RCC leads to Ca2+ influx, activation of CAMKK2, AMPK, and ULK1, and phagophore formation. In addition, TRPM3 Ca2+ and Zn2+ fluxes inhibit miR-214 which directly targets LC3A and LC3B. The von Hippel-Lindau tumor suppressor (VHL) represses TRPM3 through miR-204 directly and indirectly through another miR-204 target, Caveolin 1 (CAV1). PMID:25517751

Bleeding score in type 1 von Willebrand disease patients using the condensed MCMDM-1 vWD validated questionnaire.

PubMed

Pathare, A; Al Hajri, F; Al Omrani, S; Al Obaidani, N; Al Balushi, B; Al Falahi, K

2018-05-13

Assessment of the severity of bleeding symptom has led to the evolution of bleeding assessment tools which are now validated. To administer the condensed molecular and clinical markers for the diagnosis and management of type 1 von Willebrand disease VWD (MCMDM-1 vWD) questionnaire to the Omani type 1 vWD patients and correlate it with the laboratory parameters. Patients and controls were personally interviewed and the condensed MCMDM-1 vWD questionnaire administered by a single investigator. Bleeding score (BS) was calculated, based on the presence or absence of the bleeding symptoms according to a standard validated questionnaire in both the patients and the controls. The median age of the patient cohort was 27 (range, 7-49) years with 60.87% of females. The median time to administer condensed MCMDM-1 BS questionnaire was 11 minutes (interquartile range-IQR;7,16). Overall, bleeding from the oral cavity was the most predominant symptom (63%). The median BS was 5 (IQR;1,8) although individual scores ranged between 0 and 29. However, there was no statistically significant difference in BS between genders (males: median 4; IQR 1,6 and females: median 5, IQR 1,10) (P > .05, Kruskal-Wallis test) The Spearman's correlation value of BS was weak with FVIII:C levels and von Willebrand Ristocetin co-factor activity; very weak with von Willebrand Antigen level, and moderate with vonWillebrand Collagen Binding activity being -0.29, -0.28, -0.14 and -0.43, respectively. The BS reflects the severity of bleeding among the vWD patients. Although the BS was abnormal, it did not correlate significantly with the surrogate laboratory parameters [P > .05]. © 2018 John Wiley & Sons Ltd.

A rapid method to visualize von willebrand factor multimers by using agarose gel electrophoresis, immunolocalization and luminographic detection.

PubMed

Krizek, D R; Rick, M E

2000-03-15

A highly sensitive and rapid clinical method for the visualization of the multimeric structure of von Willebrand Factor in plasma and platelets is described. The method utilizes submerged horizontal agarose gel electrophoresis, followed by transfer of the von Willebrand Factor onto a polyvinylidine fluoride membrane, and immunolocalization and luminographic visualization of the von Willebrand Factor multimeric pattern. This method distinguishes type 1 from types 2A and 2B von Willebrand disease, allowing timely evaluation and classification of von Willebrand Factor in patient plasma. It also allows visualization of the unusually high molecular weight multimers present in platelets. There are several major advantages to this method including rapid processing, simplicity of gel preparation, high sensitivity to low concentrations of von Willebrand Factor, and elimination of radioactivity.

An Affine Invariant Bivariate Version of the Sign Test.

DTIC Science & Technology

1987-06-01

words: affine invariance, bivariate quantile, bivariate symmetry, model,. generalized median, influence function , permutation test, normal efficiency...calculate a bivariate version of the influence function , and the resulting form is bounded, as is the case for the univartate sign test, and shows the...terms of a blvariate analogue of IHmpel’s (1974) influence function . The latter, though usually defined as a von-Mises derivative of certain

Impaired diffuse noxious inhibitory controls in specific alternation of rhythm in temperature-stressed rats.

PubMed

Itomi, Yasuo; Tsukimi, Yasuhiro; Kawamura, Toru

2016-08-05

Fibromyalgia is characterized by chronic widespread musculoskeletal pain. A hypofunction in descending pain inhibitory systems is considered to be involved in the chronic pain of fibromyalgia. We examined functional changes in descending pain inhibitory systems in rats with specific alternation of rhythm in temperature (SART) stress, by measuring the strength of diffuse noxious inhibitory controls (DNIC). Hindpaw withdrawal thresholds to mechanical von Frey filament or fiber-specific electrical stimuli by the Neurometer system were used to measure the pain response. To induce DNIC, capsaicin was injected into the intraplantar of the forepaw. SART-stressed rats were established by exposure to repeated cold stress for 4 days. In the control rats, heterotopic intraplantar capsaicin injection increased withdrawal threshold, indicative of analgesia by DNIC. The strength of DNIC was reduced by naloxone (μ-opioid receptor antagonist, intraperitoneally and intracerebroventricularly), yohimbine (α2-adrenoceptor antagonist, intrathecally), and WAY-100635 (5-HT1A receptor antagonist, intrathecally) in the von Frey test. In SART-stressed rats, capsaicin injection did not increase withdrawal threshold in the von Frey test, indicating deficits in DNIC. In the Neurometer test, deficient DNIC in SART-stressed rats were observed only for Aδ- and C-fibers, but not Aβ-fibers stimulation. Analgesic effect of intracerebroventricular morphine was markedly reduced in SART-stressed rats compared with the control rats. Taken together, in SART-stressed rats, capsaicin-induced DNIC were deficient, and a hypofunction of opioid-mediated central pain modulation system may cause the DNIC deficit. Copyright © 2016 Elsevier B.V. All rights reserved.

Establishment and characterization of a new and stable collagen-binding assay for the assessment of von Willebrand factor activity

PubMed Central

Ni, Y; Nesrallah, J; Agnew, M; Geske, F J; Favaloro, E J

2013-01-01

Introduction Laboratory diagnosis of von Willebrand disease (VWD) requires determination of both von Willebrand factor (VWF) protein levels and activity. Current VWF activity tests include the ristocetin cofactor assay and the collagen-binding assay (VWF:CB). The goal of this investigation is to characterize a new collagen-binding assay and to determine its effectiveness in identifying VWD. Methods Analytical studies were carried out to characterize the performance of a new VWF:CB ELISA. Additionally, samples from a normal population were tested as were well-characterized type 1 and type 2 VWD samples. Results Repeatability and within-laboratory precision studies resulted in coefficients of variation (CVs) of ≤11%. A linear range of 1–354% (0.01–3.54 IU/mL) was determined, along with a limit of detection and a lower limit of quantitation of 1.6% and 4.0% (0.016 and 0.04 IU/mL), respectively. Samples tested from apparently healthy individuals resulted in a normal range of 54–217% (0.54–2.17 IU/mL). Known VWD type 1 and type 2 samples were also analyzed by the ELISA, with 99% of samples having VWF:CB below the normal reference range and an estimated 96% sensitivity and 87% specificity using a VWF collagen-binding/antigen cutoff ratio of 0.50. Conclusion This new VWF:CB ELISA provides an accurate measure of collagen-binding activity that aids in the diagnosis and differentiation of type 1 from type 2 VWD. PMID:23107512

Clarifying the link between von Neumann and thermodynamic entropies

NASA Astrophysics Data System (ADS)

Deville, Alain; Deville, Yannick

2013-01-01

The state of a quantum system being described by a density operator ρ, quantum statistical mechanics calls the quantity - kTr( ρln ρ), introduced by von Neumann, its von Neumann or statistical entropy. A 1999 Shenker's paper initiated a debate about its link with the entropy of phenomenological thermodynamics. Referring to Gibbs's and von Neumann's founding texts, we replace von Neumann's 1932 contribution in its historical context, after Gibbs's 1902 treatise and before the creation of the information entropy concept, which places boundaries into the debate. Reexamining von Neumann's reasoning, we stress that the part of his reasoning implied in the debate mainly uses thermodynamics, not quantum mechanics, and identify two implicit postulates. We thoroughly examine Shenker's and ensuing papers, insisting upon the presence of open thermodynamical subsystems, imposing us the use of the chemical potential concept. We briefly mention Landau's approach to the quantum entropy. On the whole, it is shown that von Neumann's viewpoint is right, and why Shenker's claim that von Neumann entropy "is not the quantum-mechanical correlate of thermodynamic entropy" can't be retained.

An investigation of the 'von Restorff' phenomenon in post-test workload ratings

NASA Technical Reports Server (NTRS)

Thornton, D. C.

1985-01-01

The von Restorff effect in post-task ratings of task difficulty is examined. Nine subjects performed a hovercraft simulation task which combined elements of skill-based tracking and rule- and knowledge-based process control for five days of one hour sessions. The effects of isolated increases in workload on rating of task performance, and on the number of command errors and river band hits are analyzed. It is observed that the position of the workload increase affects the number of bank hits and command errors. The data reveal that factors not directly related to the task performance influence subjective rating, and post-task ratings of workload are biased.

Diagnostic Genetics at a Distance: Von Hippel-Lindau Disease and a Novel Mutation

PubMed Central

Prosser, Debra O.; Love, Jennifer M.; Gardner, R. J. McKinlay; Love, Donald R.

2013-01-01

Genetic testing at a distance is commonplace where members of a family with a segregating germline mutation are geographically separated. For the most part, this challenge is addressed through the intervention of health professionals in taking and/or processing blood samples for subsequent couriering of DNA to a referral laboratory. In some circumstances, however, the collecting of pivotal clinical material may involve direct patient involvement. We describe such a situation where noninvasive saliva samples were provided by members of a family manifesting Von Hippel-Lindau (VHL) disease. The analysis identified a novel mutation in the VHL gene that was used to exclude other family members as being at risk of VHL disease. PMID:24062953

Characterization of Novel Sorghum brown midrib Mutants from an EMS-Mutagenized Population

PubMed Central

Sattler, Scott E.; Saballos, Ana; Xin, Zhanguo; Funnell-Harris, Deanna L.; Vermerris, Wilfred; Pedersen, Jeffrey F.

2014-01-01

Reducing lignin concentration in lignocellulosic biomass can increase forage digestibility for ruminant livestock and saccharification yields of biomass for bioenergy. In sorghum (Sorghum bicolor (L.) Moench) and several other C4 grasses, brown midrib (bmr) mutants have been shown to reduce lignin concentration. Putative bmr mutants isolated from an EMS-mutagenized population were characterized and classified based on their leaf midrib phenotype and allelism tests with the previously described sorghum bmr mutants bmr2, bmr6, and bmr12. These tests resulted in the identification of additional alleles of bmr2, bmr6, and bmr12, and, in addition, six bmr mutants were identified that were not allelic to these previously described loci. Further allelism testing among these six bmr mutants showed that they represented four novel bmr loci. Based on this study, the number of bmr loci uncovered in sorghum has doubled. The impact of these lines on agronomic traits and lignocellulosic composition was assessed in a 2-yr field study. Overall, most of the identified bmr lines showed reduced lignin concentration of their biomass relative to wild-type (WT). Effects of the six new bmr mutants on enzymatic saccharification of lignocellulosic materials were determined, but the amount of glucose released from the stover was similar to WT in all cases. Like bmr2, bmr6, and bmr12, these mutants may affect monolignol biosynthesis and may be useful for bioenergy and forage improvement when stacked together or in combination with the three previously described bmr alleles. PMID:25187038

Thrombin-dependent Incorporation of von Willebrand Factor into a Fibrin Network*

PubMed Central

Miszta, Adam; Pelkmans, Leonie; Lindhout, Theo; Krishnamoorthy, Ganeshram; de Groot, Philip G.; Hemker, Coenraad H.; Heemskerk, Johan W. M.; Kelchtermans, Hilde; de Laat, Bas

2014-01-01

Attachment of platelets from the circulation onto a growing thrombus is a process involving multiple platelet receptors, endothelial matrix components, and coagulation factors. It has been indicated previously that during a transglutaminase reaction activated factor XIII (FXIIIa) covalently cross-links von Willebrand factor (VWF) to polymerizing fibrin. Bound VWF further recruits and activates platelets via interactions with the platelet receptor complex glycoprotein Ib (GPIb). In the present study we found proof for binding of VWF to a fibrin monomer layer during the process of fibrinogen-to-fibrin conversion in the presence of thrombin, arvin, or a snake venom from Crotalus atrox. Using a domain deletion mutant we demonstrated the involvement of the C domains of VWF in this binding. Substantial binding of VWF to fibrin monomers persisted in the presence of the FXIIIa inhibitor K9-DON, illustrating that cross-linking via factor XIII is not essential for this phenomenon and suggesting the identification of a second mechanism through which VWF multimers incorporate into a fibrin network. Under high shear conditions, platelets were shown to adhere to fibrin only if VWF had been incorporated. In conclusion, our experiments show that the C domains of VWF and the E domain of fibrin monomers are involved in the incorporation of VWF during the polymerization of fibrin and that this incorporation fosters binding and activation of platelets. Fibrin thus is not an inert end product but partakes in further thrombus growth. Our findings help to elucidate the mechanism of thrombus growth and platelet adhesion under conditions of arterial shear rate. PMID:25381443

Wernher von Braun

NASA Image and Video Library

1959-01-01

This photograph of Dr. von Braun, shown here to the left of General Bruce Medaris, was taken in the fall of 1959, immediately prior to Medaris' retirement from the Army. At the time, von Braun and his associates worked for the Army Ballistics Missile Agency in Huntsville, Alabama. Those in the photograph have been identified as Ernst Stuhlinger, Frederick von Saurma, Fritz Mueller, Hermarn Weidner, E.W. Neubert (partially hidden), W.A. Mrazek, Karl Heimburg, Arthur Rudolph, Otto Hoberg, von Braun, Oswald Lange, Medaris, Helmut Hoelzer, Hans Maus, E.D. Geissler, Hans Heuter, and George Constan.

Identification of a His54Gln substitution in von Willebrand factor from a patient with defective binding of factor VIII.

PubMed

Rick, M E; Krizek, D M

1996-04-01

A patient with type 2N ("Normandy" variant) von Willebrand's disease is described. Her von Willebrand factor level was borderline low, while her factor VIII was markedly decreased to 7%. Her plasma von Willebrand factor demonstrated a decreased ability to complex with factor VIII in vitro, binding less than 10% when compared to normal plasma von Willebrand factor. The factor VIII released into the circulation after the patient received DDAVP had a shortened survival in vivo. Nucleotide sequence analysis revealed a T-to-A transition at nucleotide 2451 on both alleles. This transition results in a substitution of Gln for His at amino acid 54 in the mature subunit of von Willebrand factor.

Reduced gravitropic sensitivity in roots of a starch-deficient mutant of Nicotiana sylvestris

NASA Technical Reports Server (NTRS)

Kiss, J. Z.; Sack, F. D.

1989-01-01

Gravitropism was studied in seedlings of Nicotiana sylvestris Speg. et Comes wild-type (WT) and mutant NS 458 which has a defective plastid phosphoglucomutase (EC 2.7.5.1.). Starch was greatly reduced in NS 458 compared to the WT, but small amounts of starch were detected in rootcap columella cells in NS 458 by light and electron microscopy. The roots of WT are more sensitive to gravity than mutant NS 458 roots since: (1) in mutant roots, curvature was reduced and delayed in the time course of curvature; (2) curvature of mutant roots was 24-56% that of WT roots over the range of induction periods tested; (3) in intermittent-stimulation experiments, curvature of mutant roots was 37% or less than that of WT roots in all treatments tested. The perception time, determined by intermittent-stimulation experiments, was < or = 5 s for WT roots and 30-60 s for mutant roots. The growth rates for WT and NS 458 roots were essentially equal. These results and our previous results with WT and starchless mutant Arabidopsis roots (Kiss et al. 1989, Planta 177, 198-206) support the conclusions that a full complement of starch is necessary for full gravitropic sensitivity and that amyloplasts function in gravity perception. Since a presumed relatively small increase in plastid buoyant mass (N. sylvestris mutant versus Arabidopsis mutant) significantly improves the orientation of the N. sylvestris mutant roots, we suggest that plastids are the likeliest candidates to be triggering gravity perception in roots of both mutants.

Renal Cell Carcinoma Programmed Death-ligand 1, a New Direct Target of Hypoxia-inducible Factor-2 Alpha, is Regulated by von Hippel-Lindau Gene Mutation Status.

PubMed

Messai, Yosra; Gad, Sophie; Noman, Muhammad Zaeem; Le Teuff, Gwenael; Couve, Sophie; Janji, Bassam; Kammerer, Solenne Florence; Rioux-Leclerc, Nathalie; Hasmim, Meriem; Ferlicot, Sophie; Baud, Véronique; Mejean, Arnaud; Mole, David Robert; Richard, Stéphane; Eggermont, Alexander M M; Albiges, Laurence; Mami-Chouaib, Fathia; Escudier, Bernard; Chouaib, Salem

2016-10-01

Clear cell renal cell carcinomas (ccRCC) frequently display a loss of function of the von Hippel-Lindau (VHL) gene. To elucidate the putative relationship between VHL mutation status and immune checkpoint ligand programmed death-ligand 1 (PD-L1) expression. A series of 32 renal tumors composed of 11 VHL tumor-associated and 21 sporadic RCCs were used to evaluate PD-L1 expression levels after sequencing of the three exons and exon-intron junctions of the VHL gene. The 786-O, A498, and RCC4 cell lines were used to investigate the mechanisms of PD-L1 regulation. Fisher's exact test was used for VHL mutation and Kruskal-Wallis test for PD-L1 expression. If no covariate accounted for the association of VHL and PD-L1, then a Kruskal-Wallis test was used; otherwise Cochran-Mantel-Haenzsel test was used. We also used the Fligner-Policello test to compare two medians when the distributions had different dispersions. We demonstrated that tumors from ccRCC patients with VHL biallelic inactivation (ie, loss of function) display a significant increase in PD-L1 expression compared with ccRCC tumors carrying one VHL wild-type allele. Using the inducible VHL 786-O-derived cell lines with varying hypoxia-inducible factor-2 alpha (HIF-2α) stabilization levels, we showed that PD-L1 expression levels positively correlate with VHL mutation and HIF-2α expression. Targeting HIF-2α decreased PD-L1, while HIF-2α overexpression increased PD-L1 mRNA and protein levels in ccRCC cells. Interestingly, chromatin immunoprecipitation and luciferase assays revealed a direct binding of HIF-2α to a transcriptionally active hypoxia-response element in the human PD-L1 proximal promoter in 786-O cells. Our work provides the first evidence that VHL mutations positively correlate with PD-L1 expression in ccRCC and may influence the response to ccRCC anti-PD-L1/PD-1 immunotherapy. We investigated the relationship between von Hippel-Lindau mutations and programmed death-ligand 1 expression. We demonstrated that von Hippel-Lindau mutation status significantly correlated with programmed death-ligand 1 expression in clear cell renal cell carcinomas. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Liquid Biopsy zur Überwachung von Melanompatienten.

PubMed

Gaiser, Maria Rita; von Bubnoff, Nikolas; Gebhardt, Christoffer; Utikal, Jochen Sven

2018-04-01

In den letzten sechs Jahren wurden verschiedene innovative systemische Therapien zur Behandlung des metastasierten malignen Melanoms (MM) entwickelt. Die konventionelle Chemotherapie wurde durch neuartige Primärtherapien abgelöst, darunter systemische Immuntherapien (Anti-CTLA4- und Anti-PD1-Antikörper; Zulassung von Anti-PDL1-Antikörpern erwartet) und Therapien, die gegen bestimmte Mutationen gerichtet sind (BRAF, NRAS und c-KIT). Daher stehen die behandelnden Ärzte neuen Herausforderungen gegenüber, beispielsweise der Stratifizierung von Patienten für geeignete Behandlungen und der Überwachung von Langzeit-Respondern auf Progression. Folglich werden zuverlässige Methoden zur Überwachung von Krankheitsprogression oder Behandlungsresistenz benötigt. Lokalisierte und fortgeschrittene Krebserkrankungen können zur Bildung zirkulierender Tumorzellen und Tumor-DNA (ctDNA) führen, die sich in Proben von peripherem Blut nachweisen und quantifizieren lassen (Liquid Biopsy). Im Fall von Melanompatienten können die Ergebnisse von Liquid Biopsy als neuartige prädiktive Biomarker bei therapeutischen Entscheidungen hilfreich sein, insbesondere im Zusammenhang mit mutationsbasierten zielgerichteten Therapien. Die Herausforderungen bei der Anwendung der Liquid Biopsy beinhalten strikte Kriterien für den Phänotyp der zirkulierenden MM-Zellen oder ihrer Fragmente und die Instabilität von ctDNA im Blut. In diesem Übersichtsartikel diskutieren wir die Beschränkungen der Liquid Biopsy hinsichtlich ihrer Anwendung in der Routinediagnostik. © 2018 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Biaxial Testing of 2219-T87 Aluminum Alloy Using Cruciform Specimens

NASA Technical Reports Server (NTRS)

Dawicke, D. S.; Pollock, W. D.

1997-01-01

A cruciform biaxial test specimen was designed and seven biaxial tensile tests were conducted on 2219-T87 aluminum alloy. An elastic-plastic finite element analysis was used to simulate each tests and predict the yield stresses. The elastic-plastic finite analysis accurately simulated the measured load-strain behavior for each test. The yield stresses predicted by the finite element analyses indicated that the yield behavior of the 2219-T87 aluminum alloy agrees with the von Mises yield criterion.

Low-energy N-ion beam biotechnology application in the induction of Thai jasmine rice mutant with improved seed storability

NASA Astrophysics Data System (ADS)

Semsang, Nuananong; Techarang, Jiranat; Yu, Liangdeng; Phanchaisri, Boonrak

2018-06-01

Low-energy heavy-ion beam is a novel biotechnology used for mutation induction in plants. We used a low-energy N-ion beam to induce mutations in Thai jasmine rice (Oryza sativa L. cv. KDML 105) to improve the yield and seed quality. Seeds of BKOS6, a Thai jasmine rice mutant previously induced by ion beams, were re-bombarded with 60-kV-accelerated N-ions (N++N2+) to fluences of 1-2 × 1016 ions/cm2. The resulting mutant, named HyKOS21, exhibited photoperiod insensitivity, semi-dwarfness, and high yield potential. Seed storability of the mutant was studied in natural and accelerated ageing conditions and compared to that of KDML 105 and six other Thai rice varieties. In both testing conditions, HyKOS21 mutant had the highest seed storability among the tested varieties. After storage in the natural condition for 18 months, HyKOS21 had a seed germination percentage nearly two times as that of the original KDML 105. Biochemical analysis showed that the lipid peroxidation level of the mutant seeds was the lowest among those of the tested varieties. Furthermore, an expression analysis of genes encoding lipoxygenase isoenzyme (lox1, lox2, and lox3) revealed that the mutant lacked expression of lox1 and lox2 and expressed only lox3 in seeds. These results may explain the improved seed longevity of the mutant after storage. This work provides further evidence of the modification of biological materials using a low-energy ion beam to produce rice mutants with improved yield and seed storability. The benefits of this technology, to create new varieties with improved values, could serve for local economic development.

Assisted Design of Antibody and Protein Therapeutics (ADAPT)

PubMed Central

Vivcharuk, Victor; Baardsnes, Jason; Deprez, Christophe; Sulea, Traian; Jaramillo, Maria; Corbeil, Christopher R.; Mullick, Alaka; Magoon, Joanne; Marcil, Anne; Durocher, Yves; O’Connor-McCourt, Maureen D.

2017-01-01

Effective biologic therapeutics require binding affinities that are fine-tuned to their disease-related molecular target. The ADAPT (Assisted Design of Antibody and Protein Therapeutics) platform aids in the selection of mutants that improve/modulate the affinity of antibodies and other biologics. It uses a consensus z-score from three scoring functions and interleaves computational predictions with experimental validation, significantly enhancing the robustness of the design and selection of mutants. The platform was tested on three antibody Fab-antigen systems that spanned a wide range of initial binding affinities: bH1-VEGF-A (44 nM), bH1-HER2 (3.6 nM) and Herceptin-HER2 (0.058 nM). Novel triple mutants were obtained that exhibited 104-, 46- and 32-fold improvements in binding affinity for each system, respectively. Moreover, for all three antibody-antigen systems over 90% of all the intermediate single and double mutants that were designed and tested showed higher affinities than the parent sequence. The contributions of the individual mutants to the change in binding affinity appear to be roughly additive when combined to form double and triple mutants. The new interactions introduced by the affinity-enhancing mutants included long-range electrostatics as well as short-range nonpolar interactions. This diversity in the types of new interactions formed by the mutants was reflected in SPR kinetics that showed that the enhancements in affinities arose from increasing on-rates, decreasing off-rates or a combination of the two effects, depending on the mutation. ADAPT is a very focused search of sequence space and required only 20–30 mutants for each system to be made and tested to achieve the affinity enhancements mentioned above. PMID:28750054

Impact response and biomechanical analysis of the knee-thigh-hip complex in frontal impacts with a full human body finite element model.

PubMed

Ruan, Jesse S; El-Jawahri, Raed; Barbat, Saeed; Rouhana, Stephen W; Prasad, Priya

2008-11-01

Changes in vehicle safety design technology and the increasing use of seat-belts and airbag restraint systems have gradually changed the relative proportion of lower extremity injuries. These changes in real world injuries have renewed interest and the need of further investigation into occupant injury mechanisms and biomechanical impact responses of the knee-thigh-hip complex during frontal impacts. This study uses a detailed finite element model of the human body to simulate occupant knee impacts experienced in frontal crashes. The human body model includes detailed anatomical features of the head, neck, shoulder, chest, thoracic and lumbar spine, abdomen, pelvis, and lower and upper extremities. The material properties used in the model for each anatomic part of the human body were obtained from test data reported in the literature. The human body model used in the current study has been previously validated in frontal and side impacts. It was further validated with cadaver knee-thigh-hip impact tests in the current study. The effects of impactor configuration and flexion angle of the knee on biomechanical impact responses of the knee-thigh-hip complex were studied using the validated human body finite element model. This study showed that the knee flexion angle and the impact direction and shape of the impactors affected the injury outcomes of the knee-thigh-hip complex significantly. The 60 degrees flexed knee impact showed the least impact force, knee pressure, femoral von Mises stress, and pelvic von Mises stress but largest relative displacements of the Posterior Cruciate Ligament (PCL) and Anterior Cruciate Ligament (ACL). The 90 degrees flexed knee impact resulted in a higher impact force, knee pressure, femoral von Mises stress, and pelvic von Mises stress; but smaller PCL and ACL displacements. Stress distributions of the patella, femur, and pelvis were also given for all the simulated conditions.

Comparative age and growth of common snook Centropomus undecimalis (Pisces: Centropomidae) from coastal and riverine areas in Southern Mexico.

PubMed

Perera-Garcia, Martha A; Mendoza-Carranza, Manuel; Contreras-Sánchez, Wilfrido; Ferrara, Allyse; Huerta-Ortiz, Maricela; Hernández-Gómez, Raúl E

2013-06-01

Common snook Centropomus unidecimalis is an important commercial and fishery species in Southern Mexico, however the high exploitation rates have resulted in a strong reduction of its abundances. Since, the information about its population structure is scarce, the objective of the present research was to determine and compare the age structure in four important fishery sites. For this, age and growth of common snook were determined from specimens collected monthly, from July 2006 to March 2008, from two coastal (Barra Bosque and Barra San Pedro) and two riverine (San Pedro and Tres Brazos) commercial fishery sites in Tabasco, Mexico. Age was determined using sectioned saggitae otoliths and data analyzed by von Bertalanffy and Levenberg-Marquardt among others. Estimated ages ranged from 2 to 17 years. Monthly patterns of marginal increment formation and the percentage of otoliths with opaque rings on the outer edge demonstrated that a single annulus was formed each year. The von Bertalanffy parameters were calculated for males and females using linear adjustment and the non-linear method of Levenberg-Marquardt. The von Bertalanffy growth equations were FLt = 109.21(1-e-0.2(t+0.57)) for Barra Bosque, FLt = 94.56(1-e-027(t+0.485)) for Barra San Pedro, FLt = 97.15(1-e 0.17(t + 1.32)) for San Pedro and FLt = 83.77(1-e-026(t + 0.49)) for Tres Brazos. According to (Hotelling's T2, p < 0.05) test growth was significantly greater for females than for males. Based on the Chen test, von Bertalanffy growth curves were different among the study sites (RSS, p < 0.05). Based on the observed differences in growth parameters among sampling sites (coastal and riverine environments) future research need to be conducted on migration and population genetics, in order to delineate the stock structure of this population and support management programs.

Desmopressin therapy to assist the functional identification and characterisation of von Willebrand disease: differential utility from combining two (VWF:CB and VWF:RCo) von Willebrand factor activity assays?

PubMed

Favaloro, Emmanuel J; Thom, Jim; Patterson, David; Just, Sarah; Dixon, Tracy; Koutts, Jerry; Baccala, Maria; Rowell, John; Baker, Ross

2009-04-01

We performed a retrospective audit of desmopressin (DDAVP) usage to assist in the functional characterisation of von Willebrand disease (VWD). Data was evaluated for 208 patients, comprising those with VWD (Type 1 [n=160], Type 2A [n=19], Type 2M [n=10]), plus 19 individuals with haemophilia or carriers of haemophilia. Laboratory testing comprised pre- and post-DDAVP evaluation of factor VIII (FVIII:C), von Willebrand factor (VWF) antigen (VWF:Ag), VWF ristocetin cofactor (VWF:RCo) activity, VWF collagen binding (VWF:CB) activity, and in one laboratory an alternate VWF activity assay. In brief, combined usage of VWF:RCo and VWF:CB appears to provide improved functional characterisation and/or 'classification' of VWD types, in particular better differentiation of Type 2A and 2M VWD, and clearer validation of a Type 1 VWD diagnosis. Thus, (i) Type 1 VWD displayed generally good absolute and relative rises in all test parameters, although relative rises were greatest for FVIII:C and VWF:CB, and CB/Ag ratio increases overshadowed those for RCo/Ag; (ii) Type 2A VWD patients showed good absolute and relative rises in both FVIII:C and VWF:Ag, but poor absolute rises in both VWF:CB and VWF:RCo; although small rises in both CB/Ag and RCo/Ag were also observed, both ratios tended to remain below 0.7; (iii) finally, Type 2 M VWD patients generally showed good absolute and relative rises in FVIII:C, VWF:Ag and VWF:CB, but a poor absolute and relative rise in VWF:RCo; thus, there were good rises in CB/Ag ratios but little change in RCo/Ag, which tended to remain below 0.7. Future multi-centre prospective investigations are warranted to validate these findings and to investigate their therapeutic implications.

Wernher von Braun

NASA Image and Video Library

1977-06-16

Dr. Wernher von Braun served as Marshall Space Flight Center's first director from July 1, 1960 until January 27, 1970, when he was appointed NASA Deputy Associate Administrator for Planning. Following World War II, Dr. von Braun and his German colleagues arrived in the United States under Project Paper Clip to continue their rocket development work. In 1950, von Braun and his rocket team were transferred from Ft. Bliss, Texas to Huntsville, Alabama to work for the Army's rocket program at Redstone Arsenal and later, NASA's Marshall Space Flight Center. Under von Braun's leadership, Marshall developed the Saturn V launch vehicle which took Apollo astronauts to the moon. Dr. von Braun died in Alexandria, Va., on June 16, 1977, seven years after his NASA appointment. This photo was taken at the site where he was laid to rest.

Plasma Wind Tunnel Testing of Electron Transpiration Cooling Concept

DTIC Science & Technology

2017-02-28

AFRL-AFOSR-UK-TR-2017-0012 Plasma Wind Tunnel Testing of Electron Transpiration Cooling Concept Olivier Chazot INSTITUT VON KARMAN DE DYNAMIQUE DES...28-02-2017 2. REPORT TYPE Final 3. DATES COVERED (From - To) 01 Dec 2015 to 30 Nov 2016 4. TITLE AND SUBTITLE Plasma Wind Tunnel Testing of Electron ...Aeronautics and Aerospace Department B-1640 Rhode Saint Genèse Belgium Internal Ref: ARR 1605 February 2017 Plasma Wind Tunnel Testing of Electron

Hydrostatic Stress Effects in Metal Plasticity

NASA Technical Reports Server (NTRS)

Wilson, Christopher D.

1999-01-01

Since the 1940s, the theory of plasticity has assumed that hydrostatic stress does not affect the yield or postyield behavior of metals. This assumption is based on the early work of Bridgman. Bridgman found that hydrostatic pressure (compressive stress) does not affect yield behavior until a substantial amount of pressure (greater than 100 ksi) is present. The objective of this study was to determine the effect of hydrostatic tension on yield behavior. Two different specimen geometries were examined: an equal-arm bend specimen and a double edge notch specimen. The presence of a notch is sufficient to develop high enough hydrostatic tensile stresses to affect yield. The von Mises yield function, which does not have a hydrostatic component, and the Drucker-Prager yield function, which includes a hydrostatic component, were used in finite element analyses of the two specimen geometries. The analyses were compared to test data from IN 100 specimens. For both geometries, the analyses using the Drucker-Prager yield function more closely simulated the test data. The von Mises yield function lead to 5-10% overprediction of the force-displacement or force-strain response of the test specimens.

Wernher von Braun

NASA Image and Video Library

1960-01-01

Dr. Wernher von Braun served as Marshall Space Flight Center's first director from July 1, 1960 until January 27, 1970, when he was appointed NASA Deputy Associate Administrator for Plarning. Following World War II, Dr. von Braun and his German colleagues arrived in the United States under Project Paperclip to continue their rocket development work. In 1950, von Braun and his rocket team were transferred from Ft. Bliss, Texas to Huntsville, Alabama to work for the Army's rocket program at Redstone Arsenal and later, NASA's Marshall Space Flight Center. Under von Braun's leadership, Marshall developed the Saturn V launch vehicle which took Apollo astronauts to the moon.

Dr. von Braun and Army Ballistics Missile Agency (ABMA) Group

NASA Technical Reports Server (NTRS)

1959-01-01

This photograph of Dr. von Braun, shown here to the left of General Bruce Medaris, was taken in the fall of 1959, immediately prior to Medaris' retirement from the Army. At the time, von Braun and his associates worked for the Army Ballistics Missile Agency in Huntsville, Alabama. Those in the photograph have been identified as Ernst Stuhlinger, Frederick von Saurma, Fritz Mueller, Hermarn Weidner, E.W. Neubert (partially hidden), W.A. Mrazek, Karl Heimburg, Arthur Rudolph, Otto Hoberg, von Braun, Oswald Lange, Medaris, Helmut Hoelzer, Hans Maus, E.D. Geissler, Hans Heuter, and George Constan.

The Continuized Log-Linear Method: An Alternative to the Kernel Method of Continuization in Test Equating

ERIC Educational Resources Information Center

Wang, Tianyou

2008-01-01

Von Davier, Holland, and Thayer (2004) laid out a five-step framework of test equating that can be applied to various data collection designs and equating methods. In the continuization step, they presented an adjusted Gaussian kernel method that preserves the first two moments. This article proposes an alternative continuization method that…

[Precocious puberty and von Recklinghausen's disease].

PubMed

Barg, Ewa; Wikiera, Beata; Basiak, Aleksander; Głab, Ewa

2006-01-01

Von Recklinghausen's disease belongs to a group of neurocutaneous syndromes and is characterised by skin, nerve and bone abnormalities. We present a case of von Recklinghausen's disease and precocious puberty in 7-year-old boy. At the age of three café au lait spots on the skin and an incranial tumour situated near the optic chiasm--qualified as inoperable--were discovered. At the age of 7 first signs of precocious puberty appeared (pubic hair P3 and enlargement of the testes (15 ml) and penis). Laboratory measurements included: LH 7.5 mIU/ml, FSH 1.1 mIU/ml, testosterone 183 ng/ml, assessment of bone age: 9 years. The response to LHRH stimulation was characteristic for true precocious puberty (LH 15.9 mIU/ml and FSH 1.5 mIU/ml after 30 minutes). The MRI of the brain showed a tumour of the suprasellar region with compression of pituitary stalk. True precocious puberty was diagnosed. Treatment with Diphereline was introduced. At present the boy is 9 years old and has been treated with Diphereline for 16 months. The volume of the testicles has decreased to 7 ml and loss of pubic hair was noted. The MRI does not show any progression in tumour growth. The authors would like to underline the need of close observation of children with von Reclinghausen disease with regard to possibility of uncovering true precocious puberty which is critical for rapid diagnosis and introduction of correct treatment.

Stress distribution in maxillary first molar periodontium using straight pull headgear with vertical and horizontal tubes: A finite element analysis.

PubMed

Feizbakhsh, Masood; Kadkhodaei, Mahmoud; Zandian, Dana; Hosseinpour, Zahra

2017-01-01

One of the most effective ways for distal movement of molars to treat Class II malocclusion is using extraoral force through a headgear device. The purpose of this study was the comparison of stress distribution in maxillary first molar periodontium using straight pull headgear in vertical and horizontal tubes through finite element method. Based on the real geometry model, a basic model of the first molar and maxillary bone was obtained using three-dimensional imaging of the skull. After the geometric modeling of periodontium components through CATIA software and the definition of mechanical properties and element classification, a force of 150 g for each headgear was defined in ABAQUS software. Consequently, Von Mises and Principal stresses were evaluated. The statistical analysis was performed using T-paired and Wilcoxon nonparametric tests. Extension of areas with Von Mises and Principal stresses utilizing straight pull headgear with a vertical tube was not different from that of using a horizontal tube, but the numerical value of the Von Mises stress in the vertical tube was significantly reduced ( P < 0/05). On the other hand, the difference of the principal stress between both tubes was not significant ( P > 0/05). Based on the results, when force applied to the straight pull headgear with a vertical tube, Von Mises stress was reduced significantly in comparison with the horizontal tube. Therefore, to correct the mesiolingual movement of the maxillary first molar, vertical headgear tube is recommended.

A pathological study of the tongues of rabid dogs in the Philippines.

PubMed

Shiwa, Nozomi; Kimitsuki, Kazunori; Manalo, Daria Llenaresas; Inoue, Satoshi; Park, Chun-Ho

2018-06-01

During rabies virus infections, the minor salivary glands are one of the important organs for virus replication and excretion into the oral cavity. However, details of pathological findings and viral antigen distribution in the minor salivary glands remain poorly understood. In this study, we conducted pathological tests on the tongues of 71 rabid dogs in the Philippines; the minor salivary glands (von Ebner's glands, lingual glands), circumvallate papilla, autonomic ganglia, and skeletal muscles were evaluated. Inflammatory changes were observed in the von Ebner's glands of 20/71 dogs, in the circumvallate papilla of 10/71, and in the tongue muscle of 1/71. Conversely, no morphological changes were observed in the lingual glands and autonomic ganglia. Viral antigens were detected via immunohistochemistry-based methods in the cytoplasm of the acinar epithelium in the von Ebner's glands of all 71 dogs. Virus particles were confirmed in the intercellular canaliculi and acinar lumen via electron microscopy. In the autonomic ganglia, viral antigens were detected in 67/71 rabid dogs. Viral antigens were detected in the taste buds of all 71 dogs, and were distributed mainly in type II and III taste bud cells. In tongue muscle fibers, viral antigens were detected in 11/71 dogs. No virus antigens were detected in lingual glands. These findings suggest that rabies virus descends in the tongue along the glossopharyngeal nerve after proliferation in the brain, and von Ebner's glands and taste buds are one of the portals of virus excretion into the saliva in rabid dogs.

Wernher von Braun

NASA Image and Video Library

1970-02-24

In 1970 Marshall Space Flight Center (MSFC) Director Dr. Wernher von Braun (right) was reassigned to NASA Headquarters to serve as Deputy Associate Administrator for Plarning. Prior to his transfer, Dr. von Braun was honored for his career in Huntsville, Alabama, with the celebration of "Wernher von Braun Day." Among those participating were Alabama Governor Albert Brewer (left) and Alabama Senator John Sparkman (center). (Courtesy of Huntsville/Madison County Public library)

Characterization of novel sorghum brown midrib mutants from an EMS-mutagenized population

DOE PAGES

Sattler, Scott E.; Saballos, Ana; Xin, Zhanguo; ...

2014-09-02

Reducing lignin concentration in lignocellulosic biomass can increase forage digestibility for ruminant livestock and saccharification yields of biomass for bioenergy. In sorghum ( Sorghum bicolor (L.) Moench) and several other C4 grasses, brown midrib ( bmr) mutants have been shown to reduce lignin concentration. Putative bmr mutants isolated from an EMS-mutagenized population were characterized and classified based on their leaf midrib phenotype and allelism tests with the previously described sorghum bmr mutants bmr2, bmr6, and bmr12. These tests resulted in the identification of additional alleles of bmr2, bmr6,and bmr12, and, in addition, six bmr mutants were identified that were notmore » allelic to these previously described loci. Further allelism testing among these six bmr mutants showed that they represented four novel bmr loci. Based on this study, the number of bmr loci uncovered in sorghum has doubled. The impact of these lines on agronomic traits and lignocellulosic composition was assessed in a 2-yr field study. Most of the identified bmr lines showed reduced lignin concentration of their biomass relative to wild-type (WT). Effects of the six new bmr mutants on enzymatic saccharification of lignocellulosic materials were determined, but the amount of glucose released from the stover was similar to WT in all cases. Like bmr2, bmr6, and bmr12, these mutants may affect monolignol biosynthesis and may be useful for bioenergy and forage improvement when stacked together or in combination with the three previously described bmr alleles.« less

U.S. (ARRADCOM) Test Results for NATO Round-Robin Test on High Explosives

DTIC Science & Technology

1981-05-01

Round-Robin Test Hersteller: (Manufacturer) Probenbezeichnung: (sample symbol ) Fa. Dynamit Nobel AG (W-Germany) Werk Leverkusen-Schlebusch S - 1...0,050 % 0,004 % Beim Zufügen von 0,002 n KMnO,-Lösung zu einem durch Kochen mit Wasser er-. haltenem Auszug keine Entfärbung in 1 h (no...Hersteller: (manufacturer) Fa. Soc. Nationale des Poudres et Explosifs (SNPE) Poudrerie de Sorgues, Frankreich Probenbezeichnung: (sample symbol

Platelet-type von Willebrand Disease: Diagnostic Challenges. Flaws and Pitfalls Experienced in the THROMKID Quality Project.

PubMed

Maurer, M; Mesters, R; Schneppenheim, R; Knoefler, R; Streif, W

2015-05-01

Primary haemostasis defects comprise von Willebrand disease (VWD) and platelet disorders (PD). Although presenting with mild to moderate bleeding tendency in most cases, severe bleeding and blood loss may occur unexpectedly in trauma and surgery. Diagnosis of VWD and PD often remains difficult owing to the wide spectrum of clinical and laboratory manifestations. Platelet-type von Willebrand disease (PT-VWD) is frequently misdiagnosed as type 2B VWD. Discrimination between type 2B VWD and PT-VWD is crucial as treatment differs. A literature review revealed difficulties in diagnostic work-up and choice of optimal treatment of PT-VWD. Guidelines favour the therapeutic use of platelet concentrates. A telephone survey of diagnostic practice with regard to type 2B VWD/PT-VWD was conducted. The prevalence and incidence of type 2B and PT-VWD remained unclear, but PT-VWD may be underestimated. An international study estimated that PT-VWD constitutes up to 15% of the total number of patients diagnosed with type 2B VWD. Our survey confirmed difficulties with diagnosis and showed that some centres did not exclude PT-VWD in type 2B patients. Some authors emphasize that genetic testing is the gold standard for diagnosis, but functional testing allows immediate diagnosis. Due to the important therapeutic implications we suggest that type 2B VWD be confirmed by genetic testing and that in case of a negative result PT-VWD should be excluded. PT-VWD should be excluded in all suspected cases of type 2B. PT-VWD should be treated with platelet concentrates. © Georg Thieme Verlag KG Stuttgart · New York.

Phenotypic characterization of spontaneously mutated rats showing lethal dwarfism and epilepsy.

PubMed

Suzuki, Hiroetsu; Takenaka, Motoo; Suzuki, Katsushi

2007-08-01

We have characterized the phenotype of spontaneously mutated rats, found during experimental inbreeding in a closed colony of Wistar Imamichi rats. Mutant rats showed severe dwarfism, short lifespan (early postnatal lethality), and high incidence of epileptic seizures. Mutant rats showed growth retardation after 3 d of age, and at 21 d their weight was about 56% that of normal rats. Most mutant rats died without reaching maturity, and 95% of the mutant rats had an ataxic gait. About 34% of the dwarf rats experienced epileptic seizures, most of which started as 'wild running' convulsions, progressing to generalized tonic-clonic convulsions. At age 28 d, the relative weight of the testes was significantly lower, and the relative weight of the brain was significantly higher, in mutant than in normal rats. Histologically, increased apoptotic germ cells, lack of spermatocytes, and immature Leydig cells were found in the mutant testes, and extracellular vacuoles of various sizes were present in the hippocampus and amygdala of the mutant brain. Mutant rats had significantly increased concentrations of plasma urea nitrogen, creatinine, and inorganic phosphate, as well as decreased concentrations of plasma growth hormone. Hereditary analysis showed that the defects were inherited as a single recessive trait. We have named the hypothetically mutated gene as lde (lethal dwarfism with epilepsy).

Wernher von Braun

NASA Image and Video Library

2004-04-15

A pioneer of America's space program, Dr. von Braun stands by the five F-1 engines of the Saturn V launch vehicle. This Saturn V vehicle is an actual test vehicle which has been displayed at the U.S. Space Rocket Center in Huntsville, Alabama. Designed and developed by Rocketdyne under the direction of the Marshall Space Flight Center, a cluster of five F-1 engines was mounted on the Saturn V S-IC (first) stage. The engines measured 19-feet tall by 12.5-feet at the nozzle exit and burned 15 tons of liquid oxygen and kerosene each second to produce 7,500,000 pounds of thrust. The S-IC stage is the first stage, or booster, of a 364-foot long rocket that ultimately took astronauts to the Moon.

Results of aeroheating DFI and ET design-data test on a 0.0175-scale model 60-OTS conducted in the Von Karman Gas Dynamics Facility (VKF) 40" supersonic and the 50" hypersonic wind tunnels A and C

NASA Technical Reports Server (NTRS)

Marroquin, J.; Leef, C. R.

1985-01-01

The 0.0175-scale thin-skin thermocouple Model 60-OTS was tested in the von Karman Gas Facility 40-inch continuous flow supersonic tunnel A and the VKF Tunnel C. Testing was conducted at Mach numbers 2.25 to 4.0, and Reynolds numbers from 0.4 x 10 to the 6th power/ft to 6.6 x 10 to the 6th power/ft. Angle of attack range was from -5.0 to +5.0 degrees, and angle of sideslip range was from -6 to +6 degrees. The primary objective of this test was to provide a valid base for the external tank (ET) and solid rocket booster (SRB) heating prediction methodology for ascent flight by taking heating data at Development Flight Instrumentation (DFI) locations for flight conditions simulating STS-1 through -4. A second objective was to obtain additional aeroheating data to support potential reduction of the thermal protection system (TPS) on the ET. The third phase of the test was funded and conducted by NASA/MSFC for the purpose of establishing confidence in the data base from the lower temperature tunnel A.

BEHAVIORAL AND NEUROCHEMICAL CHARACTERIZATION OF THE mlh MUTANT MICE LACKING OTOCONIA.

PubMed

Manes, Marianna; Garcia-Gomes, Mariana de Souza Aranha; Sandini, Thaísa Meira; Zaccarelli-Magalhães, J; Florio, J C; Alexandre-Ribeiro, Sandra Regina; Wadt, Danilo; Bernardi, Maria Martha; Massironi, Silvia Maria Gomes; Mori, Claudia Madalena Cabrera

2018-06-15

Otoconia are crucial for the correct processing of positional information and orientation. Mice lacking otoconia cannot sense the direction of the gravity vector and cannot swim properly. This study aims to characterize the behavior of mergulhador (mlh), otoconia-deficient mutant mice. Additionally, the central catecholamine levels were evaluated to investigate possible correlations between behaviors and central neurotransmitters. A sequence of behavioral tests was used to evaluate the parameters related to the general activity, sensory nervous system, psychomotor system, and autonomous nervous system, in addition to measuring the acquisition of spatial and declarative memory, anxiety-like behavior, motor coordination, and swimming behavior of the mlh mutant mice. As well, the neurotransmitter levels in the cerebellum, striatum, frontal cortex, and hippocampus were measured. Relative to BALB/c mice, the mutant mlh mice showed 1) reduced locomotor and rearing behavior, increased auricular and touch reflexes, decreased motor coordination and increased micturition; 2) decreased responses in the T-maze and aversive wooden beam tests; 3) increased time of immobility in the tail suspension test; 4) no effects in the elevated plus maze or object recognition test; 5) an inability to swim; and 6) reduced turnover of dopaminergic system in the cerebellum, striatum, and frontal cortex. Thus, in our mlh mutant mice, otoconia deficiency reduced the motor, sensory and spatial learning behaviors likely by impairing balance. We did not rule out the role of the dopaminergic system in all behavioral deficits of the mlh mutant mice. Copyright © 2018. Published by Elsevier B.V.

Host range phenotype induced by mutations in the internal ribosomal entry site of poliovirus RNA.

PubMed Central

Shiroki, K; Ishii, T; Aoki, T; Ota, Y; Yang, W X; Komatsu, T; Ami, Y; Arita, M; Abe, S; Hashizume, S; Nomoto, A

1997-01-01

Most poliovirus strains infect only primates. The host range (HR) of poliovirus is thought to be primarily determined by a cell surface molecule that functions as poliovirus receptor (PVR), since it has been shown that transgenic mice are made poliovirus sensitive by introducing the human PVR gene into the genome. The relative levels of neurovirulence of polioviruses tested in these transgenic mice were shown to correlate well with the levels tested in monkeys (H. Horie et al., J. Virol. 68:681-688, 1994). Mutants of the virulent Mahoney strain of poliovirus have been generated by disruption of nucleotides 128 to 134, at stem-loop II within the 5' noncoding region, and four of these mutants multiplicated well in human HeLa cells but poorly in mouse TgSVA cells that had been established from the kidney of the poliovirus-sensitive transgenic mouse. Neurovirulence tests using the two animal models revealed that these mutants were strongly attenuated only in tests with the mouse model and were therefore HR mutants. The virus infection cycle in TgSVA cells was restricted by an internal ribosomal entry site (IRES)-dependent initiation process of translation. Viral protein synthesis and the associated block of cellular protein synthesis were not observed in TgSVA cells infected with three of four HR mutants and was evident at only a low level in the remaining mutant. The mutant RNAs were functional in a cell-free protein synthesis system from HeLa cells but not in those from TgSVA and mouse neuroblastoma NS20Y cells. These results suggest that host factor(s) affecting IRES-dependent translation of poliovirus differ between human and mouse cells and that the mutant IRES constructs detect species differences in such host factor(s). The IRES could potentially be a host range determinant for poliovirus infection. PMID:8985316

Forebrain-Specific Loss of BMPRII in Mice Reduces Anxiety and Increases Object Exploration.

PubMed

McBrayer, Zofeyah L; Dimova, Jiva; Pisansky, Marc T; Sun, Mu; Beppu, Hideyuki; Gewirtz, Jonathan C; O'Connor, Michael B

2015-01-01

To investigate the role of Bone Morphogenic Protein Receptor Type II (BMPRII) in learning, memory, and exploratory behavior in mice, a tissue-specific knockout of BMPRII in the post-natal hippocampus and forebrain was generated. We found that BMPRII mutant mice had normal spatial learning and memory in the Morris water maze, but showed significantly reduced swimming speeds with increased floating behavior. Further analysis using the Porsolt Swim Test to investigate behavioral despair did not reveal any differences in immobility between mutants and controls. In the Elevated Plus Maze, BMPRII mutants and Smad4 mutants showed reduced anxiety, while in exploratory tests, BMPRII mutants showed more interest in object exploration. These results suggest that loss of BMPRII in the mouse hippocampus and forebrain does not disrupt spatial learning and memory encoding, but instead impacts exploratory and anxiety-related behaviors.

Forebrain-Specific Loss of BMPRII in Mice Reduces Anxiety and Increases Object Exploration

PubMed Central

McBrayer, Zofeyah L.; Dimova, Jiva; Pisansky, Marc T.; Sun, Mu; Beppu, Hideyuki; Gewirtz, Jonathan C.; O’Connor, Michael B.

2015-01-01

To investigate the role of Bone Morphogenic Protein Receptor Type II (BMPRII) in learning, memory, and exploratory behavior in mice, a tissue-specific knockout of BMPRII in the post-natal hippocampus and forebrain was generated. We found that BMPRII mutant mice had normal spatial learning and memory in the Morris water maze, but showed significantly reduced swimming speeds with increased floating behavior. Further analysis using the Porsolt Swim Test to investigate behavioral despair did not reveal any differences in immobility between mutants and controls. In the Elevated Plus Maze, BMPRII mutants and Smad4 mutants showed reduced anxiety, while in exploratory tests, BMPRII mutants showed more interest in object exploration. These results suggest that loss of BMPRII in the mouse hippocampus and forebrain does not disrupt spatial learning and memory encoding, but instead impacts exploratory and anxiety-related behaviors. PMID:26444546

UV-induced lethal sectoring and pure mutant clones in yeast.

PubMed

Hannan, M A; Duck, P; Nasim, A

1976-08-01

The induction of lethal sectoring and pure mutant clones by ultraviolet light has been studied in a homogeneous G1 population of Saccharomyces cerevisiae grown in a normal growth medium. At the lowest UV dose of 250 ergs, which corresponds to a shoulder in the survival curve, all mutants appeared as pure clones. At higher doses the frequency of mosaic mutants progressively increased. These results indicate a relationship between the highest frequency of complete mutants and the maximum repair activity. In addition, the frequency of lethal sectoring at all doses tested was too low to account for the origin of pure mutant clones.

Detection of BRAF mutations from solid tumors using Tumorplex™ technology

PubMed Central

Yo, Jacob; Hay, Katie S.L.; Vinayagamoorthy, Dilanthi; Maryanski, Danielle; Carter, Mark; Wiegel, Joseph; Vinayagamoorthy, Thuraiayah

2015-01-01

Allele specific multiplex sequencing (Tumorplex™) is a new molecular platform for the detection of single base mutation in tumor biopsies with high sensitivity for clinical testing. Tumorplex™ is a novel modification of Sanger sequencing technology that generates both mutant and wild type nucleotide sequences simultaneously in the same electropherogram. The molecular weight of the two sequencing primers are different such that the two sequences generated are separated, thus eliminating possible suppression of mutant signal by the more abundant wild type signal. Tumorplex™ platform technology was tested using BRAF mutation V600E. These studies were performed with cloned BRAF mutations and genomic DNA extracted from tumor cells carrying 50% mutant allele. The lower limit of detection for BRAF V600E was found to be 20 genome equivalents (GE) using genomic DNA extracted from mutation specific cell lines. Sensitivity of the assay was tested by challenging the mutant allele with wild type allele at 20 GE, and was able to detect BRAF mutant signal at a GE ration of 20:1 × 107 (mutant to wild-type). This level of sensitivity can detect low abundance of clonal mutations in tumor biopsies and eliminate the need for cell enrichment. • Tumorplex™ is a single tube assay that permits the recognition of mutant allele without suppression by wildtype signal. • Tumorplex™ provides a high level of sensitivity. • Tumorplex™ can be used with small sample size with mixed population of cells carrying heterogeneous gDNA. PMID:26258049

Mercury Project

NASA Image and Video Library

1961-03-24

The Mercury-Redstone Booster Development vehicle (MR-BD) lifts off from Cape Canaveral March 24, 1961. This test flight evaluated changes incorporated in the booster designed to reduce vehicle oscillations and vibrations. The Mercury-Redstone launch vehicle was developed by Dr. Wernher von Braun and the rocket team in Huntsville, Alabama.

Traumatic Coagulopathy: Where are the Good Experimental Models?

DTIC Science & Technology

2008-10-01

XM, Tevaearai HT, Jegger D, Tucker O, von Segesser LK. Are standard human coagulation tests suitable in pigs and calves during extracorporeal ... circulation ? Artif Organs. 2001;25:579–584. 44. Karges HE, Funk KA, Ronneberger H. Activity of coagulation and fibrinolysis parameters in animals

Dr. von Braun Briefing Walt Disney

NASA Technical Reports Server (NTRS)

1965-01-01

Dr. von Braun began his association with Walt Disney in the 1950s when the rocket scientist appeared in three Disney television productions related to the exploration of space. Years later, Dr. von Braun invited Disney and his associates to tour the Marshall Space Flight Center (MSFC) in Huntsville, Alabama. This photograph is dated April 13, 1965. From left are R.J. Schwinghamer from the MSFC, Disney, B.J. Bernight, and Dr. von Braun.

Wernher von Braun

NASA Image and Video Library

1954-01-01

Marshall Center Director Dr. Wernher Von Braun is pictured with Walt Disney during a visit to the Marshall Space Flight Center in 1954. In the 1950s, Dr. Von Braun while working in California on the Saturn project, also worked with Disney studios as a technical director in making three films about Space Exploration for television. Disney's tour of Marshall in 1965 was Von Braun's hope for a renewed public interest in the future of the Space Program at NASA.

Dr. Wernher von Braun

NASA Technical Reports Server (NTRS)

2004-01-01

Dr. von Braun is looking out from a 10th floor window of building 4200 at the Marshall Space Flight Center (MSFC). He was the first Center Director and served as the Director from July 1960 through February 1970. Following World War II, Dr. von Braun and his German colleagues arrived in the United States under the Project Paperclip (American acquisition of German rocket experts) to continue their rocket development work. In 1950, von Braun and his German Rocket Team (also called the Peenemuende Team) were transferred from Ft. Bliss, Texas to Huntsville, Alabama to work for the Army's rocket program at Redstone Arsenal and later, NASA's Marshall Space Flight Center (MSFC). Under Dr. von Braun's leadership, MSFC developed the Saturn V launch vehicle, which placed the first men, two American astronauts, on the Moon. Wernher von Braun's life was dedicated to expanding man's knowledge through the exploration of space.

Monte Carlo turbulence simulation using rational approximations to von Karman spectra

NASA Technical Reports Server (NTRS)

Campbell, C. W.

1986-01-01

Turbulence simulation is computationally much simpler using rational spectra, but turbulence falls off as f exp -5/3 in frequency ranges of interest to aircraft response and as predicted by von Karman's model. Rational approximations to von Karman spectra should satisfy three requirements: (1) the rational spectra should provide a good approximation to the von Karman spectra in the frequency range of interest; (2) for stability, the resulting rational transfer function should have all its poles in the left half-plane; and (3) at high frequencies, the rational spectra must fall off as an integer power of frequency, and since the -2 power is closest to the -5/3 power, the rational approximation should roll off as the -2 power at high frequencies. Rational approximations to von Karman spectra that satisfy these three criteria are presented, along with spectra from simulated turbulence. Agreement between the spectra of the simulated turbulence and von Karman spectra is excellent.

An Evaluation of the Kernel Equating Method: A Special Study with Pseudotests Constructed from Real Test Data. Research Report. ETS RR-06-02

ERIC Educational Resources Information Center

von Davier, Alina A.; Holland, Paul W.; Livingston, Samuel A.; Casabianca, Jodi; Grant, Mary C.; Martin, Kathleen

2006-01-01

This study examines how closely the kernel equating (KE) method (von Davier, Holland, & Thayer, 2004a) approximates the results of other observed-score equating methods--equipercentile and linear equatings. The study used pseudotests constructed of item responses from a real test to simulate three equating designs: an equivalent groups (EG)…

Mercury Project

NASA Image and Video Library

1961-01-01

Ham, a three-year-old chimpanzee, in the spacesuit he would wear for the second Mercury- Redstone (MR-2) suborbital test flight in January, 1961. NASA used chimpanzees and other primates to test the Mercury capsule before launching the fisrt American astronaut, Alan Shepard, in May 1961. The Mercury capsule rode atop a modified Redstone rocket, developed by Dr. Wernher von Braun and the German Rocket Team in Huntsville, Alabama.

Ham in Spacesuit

NASA Technical Reports Server (NTRS)

1961-01-01

Ham, a three-year-old chimpanzee, in the spacesuit he would wear for the second Mercury- Redstone (MR-2) suborbital test flight in January, 1961. NASA used chimpanzees and other primates to test the Mercury capsule before launching the fisrt American astronaut, Alan Shepard, in May 1961. The Mercury capsule rode atop a modified Redstone rocket, developed by Dr. Wernher von Braun and the German Rocket Team in Huntsville, Alabama.

Gebrauch von Komplementärmedizin bei Patienten mit metastasierendem Melanom unter Therapie mit Ipilimumab innerhalb einer klinischen Studie.

PubMed

Huebner, Jutta; Mohr, Peter; Simon, Jan-Christoph; Fluck, Michael; Berking, Carola; Zimmer, Lisa; Loquai, Carmen

2016-05-01

In Deutschland wenden 40-90 % aller Krebspatienten Methoden der komplementären and alternativen Medizin (KAM) an. Bis dato gibt es kein Datenmaterial zum Einsatz der KAM bei Melanompatienten. Das Ziel unserer Studie war es, Daten über den Gebrauch, die Informationsquellen und Ziele von Patienten mit metastasierendem Melanom zu erfassen. Einhundertsechsundfünfzig Patienten aus 25 Studienzentren nahmen an der DecOG-MM-PAL Multibasket Studie teil. Die beteiligten Personen wurden auch gebeten, an einer Nebenstudie teilzunehmen, die ihren Gebrauch von KAM erfassen sollte. Dazu wurde während der Behandlung ein standardisierter Fragebogen zu genau festgelegten Zeitpunkten ausgeteilt. Insgesamt gingen 55 Fragebögen von 32 (21 %) Melanompatienten ein. Von diesen gaben 17 (53 %) ein Interesse an KAM an, und sieben (22 %) machten von KAM Gebrauch. Die Hauptinformationsquellen (31 %) waren Familienmitglieder und Freunde, gefolgt von Ärzten (19 %). Die Hauptgründe für die Anwendung von KAM waren die Stärkung des Immunsystems (41 %) und des Körpers (34 %). Nahrungsergänzungsmittel (Vitamine und Spurenelemente) wurden am häufigsten angewendet (28 %). Eine relativ hohe Anzahl an Patienten mit metastasierendem Melanom machte trotz Teilnahme an einer klinischen Studie von KAM Gebrauch. Wechselwirkungen könnten durch biologisch basierte KAM auftreten, und hier besonders bei immunmodulierenden KAM- Strategien. Um Risiken zu vermeiden, sollte die Kommunikation zwischen den Ärzten und den Patienten verbessert werden. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Titanisierung von Implantatoberflächen

NASA Astrophysics Data System (ADS)

Zimmermann, Hanngörg; Heinlein, Markus; Guldner, Norbert W.

Titan gilt seit Jahrzehnten als einer der wichtigsten Implantatwerkstoffe in der Medizin. Neben den guten mechanischen Eigenschaften (Leichtigkeit, hohe Festigkeit etc.), besitzen Titanimplantate vor allem eine hervorragende Körperverträglichkeit, so dass die Implantate optimal in den humanen Organismus integriert werden [1]. Ist jedoch aufgrund der Anforderungen an das Implantat eine hohe Flexibilität und/ oder Elastizität gefragt, so scheidet der Werkstoff Titan aufgrund seiner spröden und unflexiblen Materialeigenschaften aus. Die Folge ist der Einsatz von Implantatmaterialien, sowohl künstlichen als auch biologischen Ursprungs, welche nicht selten eine unzureichende Biokompatibilität aufweisen und somit zu Fremdköper- und immunologischen Reaktionen und Einkapselung des Implantates führen können. Die Erhöhung der Körperverträglichkeit, eine Adaption an das biologische Umfeld und eine hohe Biokompatibilität sind demzufolge die wichtigsten Eigenschaften bei der bedarfsgerechten Herstellung von Implantaten und Implantatoberflächen. Zur Gestaltung von innovativen, biokompatiblen Oberflächen stehen unterschiedliche technische Lösungsansätze zur Verfügung. Zum einen besteht die Möglichkeit, geeignete Oberflächeneigenschaften aus dem Grundmaterial selbst zu optimieren. Dies geschieht unter anderem durch Modifikation der Werkstoffoberflächen in Form von Texturierungen und Oberflächenrauhigkeiten. Zum anderen können die Oberflächeneigenschaften unabhängig von denen des Trägermaterials gestaltet werden. Durch Funktionalisierung der Oberflächen mit geeigneten Beschichtungen oder der Zugabe von Medikamenten (Drug Eluting) werden die Kunststoffimplantate dahingehend verändert, dass eine Steigerung der Körperakzeptanz erreicht wird. Die Titanbeschichtung von Implantatoberflächen kombiniert die positiven Materialeigenschaften von Titan und Polymer.

PCR-Restriction Fragment Length Polymorphism for Rapid, Low-Cost Identification of Isoniazid-Resistant Mycobacterium tuberculosis▿

PubMed Central

Caws, Maxine; Tho, Dau Quang; Duy, Phan Minh; Lan, Nguyen Thi Ngoc; Hoa, Dai Viet; Torok, Mili Estee; Chau, Tran Thi Hong; Van Vinh Chau, Nguyen; Chinh, Nguyen Tran; Farrar, Jeremy

2007-01-01

PCR-restriction fragment length poymorphism (PCR-RFLP) is a simple, robust technique for the rapid identification of isoniazid-resistant Mycobacterium tuberculosis. One hundred consecutive isolates from a Vietnamese tuberculosis hospital were tested by MspA1I PCR-RFLP for the detection of isoniazid-resistant katG_315 mutants. The test had a sensitivity of 80% and a specificity of 100% against conventional phenotypic drug susceptibility testing. The positive and negative predictive values were 1 and 0.86, respectively. None of the discrepant isolates had mutant katG_315 codons by sequencing. The test is cheap (less than $1.50 per test), specific, and suitable for the rapid identification of isoniazid resistance in regions with a high prevalence of katG_315 mutants among isoniazid-resistant M. tuberculosis isolates. PMID:17428939

John von Neumann and Klaus Fuchs: an Unlikely Collaboration

NASA Astrophysics Data System (ADS)

Bernstein, Jeremy

2010-03-01

I discuss the origin of the idea of making a fusion (hydrogen) bomb and the physics involved in it, and then turn to the design proposed for one by the unlikely collaborators John von Neumann and Klaus Fuchs in a patent application they filed at Los Alamos in May 1946, which Fuchs passed on to the Russians in March 1948, and which with substantial modifications was tested on the island of Eberiru on the Eniwetok atoll in the South Pacific on May 8, 1951. This test showed that the fusion of deuterium and tritium nuclei could be ignited, but that the ignition would not propagate because the heat produced was rapidly radiated away. Meanwhile, Stanislaw Ulam and C.J. Everett had shown that Edward Teller’s Classical Super could not work, and at the end of December 1950, Ulam had conceived the idea of super compression, using the energy of a fission bomb to compress the fusion fuel to such a high density that it would be opaque to the radiation produced. Once Teller understood this, he invented a greatly improved, new method of compression using radiation, which then became the heart of the Ulam-Teller bomb design, which was tested, also in the South Pacific, on November 1, 1952. The Russians have freely acknowledged that Fuchs gave them the fission bomb, but they have insisted that no one gave them the fusion bomb, which grew out of design involving a fission bomb surrounded by alternating layers of fusion and fission fuels, and which they tested on November 22, 1955. Part of the irony of this story is that neither the American nor the Russian hydrogen-bomb programs made any use of the brilliant design that von Neumann and Fuchs had conceived as early as 1946, which could have changed the entire course of development of both programs.

A short history of diagnostic tests for von Willebrand disease: in memory of Barry Firkin (1930 to 2001) and Ted Zimmerman (1937 to 1988).

PubMed

Koutts, Jerry

2006-07-01

By the end of the 1960s, von Willebrand disease (vWD) was accepted as a combined deficiency of factor (F) VIII coagulation and a plasma factor responsible for normal platelet adhesion. Just how these two functions related to each other was unclear, and the diagnostic tests available at the time were poorly reproducible, cumbersome, and unreliable. As a consequence, the condition was poorly delineated from other coagulation and platelet disorders. In the early 1970s, ristocetin-induced platelet aggregation was described and formed the basis of the first consistent and reliable test that quantified the platelet adhesive function missing in vWD. Immunoprecipitating techniques specific for the molecule missing in vWD were defined. The application of these technologies allowed a clearer understanding of the heterogeneity of vWD and continues to form a basis for the diagnosis of this condition. Concurrently, exploration of the structure and function of von Willebrand factor (vWF) has contributed greatly to the understanding of platelet physiology, ligand receptor interaction, and pathways of cellular interaction and activation. Despite all of the progress during the last 35 years, including extensive developments in the field of molecular biology and genetics of vWD, the diagnosis of this condition in many, if not most cases, remains controversial. The final plasma level of vWF is influenced substantially by epigenetic and environmental factors. This natural heterogeneity is further compounded by significant imprecision of existing tests. As a consequence, defining vWD on the basis of a variation from the normal range alone is more than likely to be incorrect. The high frequency of a positive bleeding disorder in the normal population does not assist discrimination. It has been suggested that the diagnosis of mild type 1 vWD be discarded because it does not exhibit consistent linkage to the VWF gene and does not predict bleeding.

Ein Konzept für den energieeffizienten Betrieb von Mobilfunknetzen

NASA Astrophysics Data System (ADS)

Bayer, N.; von Hugo, D.

2015-11-01

Der flächendeckende Betrieb mehrerer Mobilfunknetze unterschiedlicher Technologie in einem Land sorgt aufgrund der ständigen Bereithaltung von Übertragungskapazität für Dienste mit zunehmend höherem Datenvolumenbedarf für einen erheblichen Energieverbrauch. Das Forschungsförderungsprojekt ComGreen hat sich zur Aufgabe gesetzt, durch lastadaptiven Betrieb und intelligente dynamische Rekonfiguration des Funkzugangsnetzes zur Energieeinsparung beizutragen. Konzept, Herausforderungen, ausgewählte Ergebnisse von Simulationen und prototypischem Betrieb werden ebenso wie typische Erwartungswerte des künftigen Energieverbrauchs im Mobilfunkbereich vorgestellt. Sowohl Berechnungen als auch Messungen zeigen, dass durch kontext-basierte dynamische Rekonfiguration von zellularen Funknetzen Energieeinsparungen im Bereich von 25-40 % ermöglicht werden.

Versuche zur Gewinnung von katalytischen Antikörpern zur Hydrolyse von Arylcarbamaten und Arylharnstoffen. (English Title: Attempts to produce catalytic antibodies for hydrolysis of arylcarbamates and arylureas)

NASA Astrophysics Data System (ADS)

Werner, Deljana

2002-05-01

Im Rahmen dieser Arbeit gelang es, katalytische Antikörper zur Hydrolyse von Benzylphenylcarbamaten sowie zahlreiche monoklonale Antikörper gegen Haptene herzustellen. Es wurden verschiedene Hapten-Protein-Konjugate unter Verwendung unterschiedlicher Kopplungsmethoden hergestellt und charakterisiert. Zur Generierung der hydrolytisch aktiven Antikörper wurden Inzuchtmäuse mit KLH-Konjugaten von 4 Übergangszustandsanaloga (ÜZA) immunisiert. Mit Hilfe der Hybridomtechnik wurden verschiedene monoklonale Antikörper gegen diese ÜZA gewonnen. Dabei wurden sowohl verschiedene Immunisierungsschemata als auch verschiedene Inzuchtmausstämme und Fusionstechniken verwendet. Insgesamt wurden 32 monoklonale Antikörper gegen die verwendeten ÜZA selektiert. Diese Antikörper wurden in groen Mengen hergestellt und gereinigt. Zum Nachweis der Antikörper-vermittelten Katalyse wurden verschiedene Methoden entwickelt und eingesetzt, darunter immunologische Nachweismethoden mit Anti-Substrat- und Anti-Produkt-Antikörpern und eine photometrische Methode mit Dimethylaminozimtaldehyd. Der Nachweis der hydrolytischen Aktivität gelang mit Hilfe eines Enzymsensors, basierend auf immobilisierter Tyrosinase. Die Antikörper N1-BC1-D11, N1-FA7-C4, N1-FA7-D12 und R3-LG2-F9 hydrolysierten die Benzylphenylcarbamate POCc18, POCc19 und Substanz 27. Der Nachweis der hydrolytischen Aktivität dieser Antikörper gelang auch mit Hilfe der HPLC. Der katalytische Antikörper N1-BC1-D11 wurde kinetisch und thermodynamisch untersucht. Es wurde eine Michaelis-Menten-Kinetik mit Km von 210 µM, vmax von 3 mM/min und kcat von 222 min-1 beobachtet. Diese Werte korrelieren mit den Werten der wenigen bekannten Diphenylcarbamat-spaltenden Abzyme. Die Beschleunigungsrate des Antikörpers N1-BC1-D11 betrug 10. Das ÜZA Hei3 hemmte die hydrolytische Aktivität. Dies beweist, dass die Hydrolyse in der Antigenbindungsstelle stattfindet. Weiter wurde zwischen der Antikörperkonzentration und der Umsatzgeschwindigkeit eine lineare Abhängigkeit festgestellt. Die thermodynamische Gleichtgewichtsdissoziationskonstante KD des Abzyms von 2,6 nM zeugt von einer sehr guten Affinität zum ÜZA. Hydrolytisch aktiv waren nur Antikörper, die gegen das Übergangszustandsanalogon Hei3 hergestellt worden waren. Es wird vermutet, dass die Hydrolyse der Benzylphenylcarbamate über einen Additions-Eliminierungsmechanismus unter Ausbildung eines tetraedrischen Übergangszustandes verläuft, dessen analoge Verbindung Hei3 ist. Im Rahmen der Generierung von Nachweisantikörpern zur Detektion der Substratabnahme bei der Hydrolyse wurden Anti-Diuron-Antikörper hergestellt. Einer der Antikörper (B91-CG5) ist spezifisch für das Herbizid Diuron und hat einen IC50-Wert von 0,19 µg/l und eine untere Nachweisgrenze von 0,04 µg/l. Ein anderer Antikörper (B91-KF5) reagiert kreuz mit einer Palette ähnlicher Herbizide. Mit diesen Antikörpern wurde ein empfindlicher Labortest, der ein Monitoring von Diuron auf Grundlage des durch die Trinkwasserverordnung festgeschriebenen Wertes für Pflanzenschutzmittel von 0,1 µg/l erlaubt, aufgebaut. Der Effekt der Anti-Diuron-Antikörper auf die Diuron-inhibierte Photosynthese wurde in vitro und in vivo untersucht. Es wurde nachgewiesen, dass sowohl in isolierten Thylakoiden, als auch in intakten Algen eine Vorinkubation der Anti-Diuron-Antikörper mit Diuron zur Inaktivierung seiner Photosynthese-hemmenden Wirkung führt. Wurde der Elektronentransport in den isolierten Thylakoiden oder in Algen durch Diuron unterbrochen, so führte die Zugabe der Anti-Diuron-Antikörper zur Reaktivierung der Elektronenübertragung. Attempts to produce catalytic antibodies for hydrolysis of arylcarbamates and arylureas: The aim of the investigations was to produce antibodies which are able to cleave herbicides resistant to naturally occuring enzymes. Structurally similar carbamate and urea derivatives were chosen for the experiments. Phosphonate derivatives were synthesized that mimick possible transition state analogues in structure and charge. Mice were immunized with 4 different derivatives after conjugating them to carrier proteins. 32 hybridomas were established that produce monoclonal antibodies binding to these derivatives. The possible cleavage of substrates was determined by immunoassays with monoclonal antibodies against the substrate and the products and with a photometric method based on dimethylaminocinammonaldehyde. The measuring of cleavage products was succeeded by an amperometric method. The enzyme sensor was based on immobilized tyrosinase which oxidizes p-chlorophenol and phenol. The antibodies N1-BC1-D11, N1-FA7-C4, N1-FA7-D12 und R3-LG2-F9 hydrolysed the benzylphenylcarbamates POCc18, POCc19 und Substance 27. The hydrolytic activity of these antibodies was also succeeded with HPLC. The catalytic antibody N1-BC1-D11 was investigated kinetically and thermodynamically. A Michaelis-Menten-Kinetic was observed (at pH 8.0 exhibited a Km 210 µM, a vmax 3 mM/min and a kcat 222 min-1). These values are in the range of the values obtained for the antibody-catalysed hydrolysis of diphenylcarbamates. The rate enhancement of N1-BC1 was 10. The reaction was completely inhibited by stoichiometric quantities of the transition state analogue Hei3. This is consistent with the affinity of the abzyme to Hei3 of 2.6 nM, determined by BIAcore assay. Only antibodies generated against Hei3 showed hydrolytic activity. The hydrolysis of benzylphenylcarbamates presumably occurs via an addition-elimination-Mechanism involving a tetrahedral intermediate. In summary, this work presents the first example of antibody-catalysed hydrolysis of benzylphenylcarbamates. Monoclonal anti-diuron antibodies were generated that bind to the herbicide diuron with an extremely low equilibrium dissociation constant. A sensitive immunoassay with a low detection limit of 0.2 nM for diuron was established. This is the most sensitive immunological method for detection of diuron known so far. These antibodies were also used in vitro and in vivo to prevent diuron-dependent inhibition of photosynthesis or to restore photosynthesis after inhibition. In isolated thylakoids prepared from spinach leaves (Spinacia oleracea L.) the diuron-inhibited Hill reaction was reconstituted immediately following the addition of the monoclonal antibodies. In an in vivo approach the photosynthetic oxygen evolution of the cell wall deficient mutant (cw 15) of the green alga Chlamydomonas reinhardtii Dangeard was monitored. The antibodies prevented the diuron-dependent inhibition of photosynthesis and restored photosynthesis after inhibition. Transgenic plants that synthesize and accumulate these antibodies or antibody fragments and are therefore diuron-resistant can be created.

Die nuklearen Anlagen von Hanford (1943-1987) Eine Fallstudie über die Schnittstellen von Physik, Biologie und die US-amerikanische Gesellschaft zur Zeit des Kalten Krieges

NASA Astrophysics Data System (ADS)

Macuglia, Daniele

Die Geschichte des Kalten Krieges eröffnet viele Möglichkeiten, sich näher mit den Schnittstellen von Physik und Biologie während des 20. Jahrhunderts zu befassen. Nicht nur das Unglück in Tschernobyl aus dem Jahr 1986, auch das Beispiel der nuklearen Anlagen in Hanford in den Vereinigten Staaten zeigt die biologischen Folgen von nuklearer Physik.

The Influence of Field Marshal Colmar Von Der Goltz on Ottoman Military Effectiveness in Mesopotamia: December 1915 to April 1916

DTIC Science & Technology

2012-02-23

SUBTITLE The Influence of Field Marshal Colmar Von Der Goltz on Ottoman Military Effectiveness in Mesopotamia: December 1915 to April 1916 5a...SUPPLEMENTARY NOTES N/A 14. ABSTRACT This paper discusses the contributions made by Field Marshal Colmar von der Goltz on the development of Ottoman...Kut. 15. SUBJECT TERMS Colmar von der Goltz ; Military advisor; Mesopotamian Campaign; Ottoman; Ottoman military effectiveness; British; Kut; World

Platelet-independent adhesion of calcium-loaded erythrocytes to von Willebrand factor

PubMed Central

Bierings, Ruben; Meems, Henriet; Mul, Frederik P. J.; Geerts, Dirk; Vlaar, Alexander P. J.; Voorberg, Jan; Hordijk, Peter L.

2017-01-01

Adhesion of erythrocytes to endothelial cells lining the vascular wall can cause vaso-occlusive events that impair blood flow which in turn may result in ischemia and tissue damage. Adhesion of erythrocytes to vascular endothelial cells has been described in multiple hemolytic disorders, especially in sickle cell disease, but the adhesion of normal erythrocytes to endothelial cells has hardly been described. It was shown that calcium-loaded erythrocytes can adhere to endothelial cells. Because sickle erythrocyte adhesion to ECs can be enhanced by ultra-large von Willebrand factor multimers, we investigated whether calcium loading of erythrocytes could promote binding to endothelial cells via ultra-large von Willebrand factor multimers. We used (immunofluorescent) live-cell imaging of washed erythrocytes perfused over primary endothelial cells at venular flow rate. Using this approach, we show that calcium-loaded erythrocytes strongly adhere to histamine-stimulated primary human endothelial cells. This adhesion is mediated by ultra-large von Willebrand factor multimers. Von Willebrand factor knockdown or ADAMTS13 cleavage abolished the binding of erythrocytes to activated endothelial cells under flow. Platelet depletion did not interfere with erythrocyte binding to von Willebrand factor. Our results reveal platelet-independent adhesion of calcium-loaded erythrocytes to endothelium-derived von Willebrand factor. Erythrocyte adhesion to von Willebrand factor may be particularly relevant for venous thrombosis, which is characterized by the formation of erythrocyte-rich thrombi. PMID:28249049

[Construction and stress tolerance of trehalase mutant in Saccharomyces cerevisiae].

PubMed

Lv, Ye; Xiao, Dongguang; He, Dongqin; Guo, Xuewu

2008-10-01

Accumulation of trehalose is critical in improving the stress tolerance of Saccharomyces cerevisiae. Two enzymes are capable of hydrolyzing trehalose: a neutral trehalase (NTH1) and an acidic trehalase (ATH1). We constructed trehalase disruption mutants to provide a basis for future commercial application. To retain the accumulation of trehalose in yeast cell, we constructed diploid homozygous neutral trehalase mutants (Deltanth1), acid trehalase mutants (Deltaath1) and double mutants (Deltaath1Deltanth1) by using gene disruption. We tested mutants'trehalose content and their tolerance to freezing, heat, high-sugar and ethanol concentrations. These trehalase disruption mutants were further confirmed by PCR amplification and southern blot. All mutant strains accumulated higher levels of cellular trehalose and grew to a higher cell density than the isogenic parent strain. In addition, the levels of trehalose in these mutants correlated with increased tolerance to freezing, heat, high-sugar and ethanol concentration. The improved tolerance of trehalase mutants may make them useful in commercial applications, including baking and brewing protein.

Isolation and preliminary characterization of temperature-sensitive mutants of influenza virus.

PubMed

Sugiura, A; Tobita, K; Kilbourne, E D

1972-10-01

Isolation of temperature-sensitive (ts) mutants was attempted from the WSN strain of influenza A virus which was grown and assayed in MDBK cells. After growth of wild-type virus in the presence of 5-fluorouracil, 15 ts mutants were selected for which the ratio of plaquing efficiency at 39.5 C to that at 33 C was 10(-3) or less. In pairwise crosses of ts mutants, recombination and complementation were either very efficient or undetectable. It is suggested, therefore, that the viral genome consists of physically discrete units and recombination occurs as an exchange of these units. All 15 mutants have been assigned with certainty into five recombination groups. Three mutants are suspected to be double mutants. Any two complementing mutants always recombined with each other, and noncomplementing mutants did not recombine. In physiological tests, mutants showed diverse patterns of functional defects at the nonpermissive temperature. However, it was not always possible to correlate these physiological defects with the results of genetic characterization.

Final Environmental Assessment: Base-Wide Building Demolition Arnold Air Force Base, Tennessee

DTIC Science & Technology

2006-02-01

Building • Engine Test Facility ( ETF )-B Exhauster • ETF -A Airside • ETF -A Exhauster • ETF -A Reefer • CE Facility • Rocket Storage • Von Karman Gas...Executive Order ESA Endangered Species Act ETF Engine Test Facility FamCamp Family Camping Area P:\\ARNOLDAFB\\333402DO42COMPLIANCE\\DEMOLITION...Fabrication Shop • Natural Resources Building • Salt Storage Building • Administration Building • Engine Test Facility ( ETF )-B Exhauster • ETF -A

Flow and fracture behavior of NiAl in relation to the brittle-to-ductile transition temperature

NASA Technical Reports Server (NTRS)

Noebe, R. D.; Bowman, R. R.; Cullers, C. L.; Raj, S. V.

1991-01-01

NiAl has only three independent slip systems operating at low and intermediate temperatures whereas five independent deformation mechanisms are required to satisfy the von Mises criterion for general plasticity in polycrystalline materials. Yet, it is generally recognized that polycrystalline NiAl can be deformed extensively in compression at room temperature and that limited tensile ductility can be obtained in extruded materials. In order to determine whether these results are in conflict with the von Mises criterion, tension and compression tests were conducted on powder-extruded, binary NiAl between 300 and 1300 K. The results indicate that below the brittle-to-ductile transition temperature (BDTT) the failure mechanism in NiAl involves the initiation and propagation of cracks at the grain boundaries which is consistent with the von Mises analysis. Furthermore, evaluation of the flow behavior of NiAl indicates that the transition from brittle to ductile behavior with increasing temperature coincides with the onset of recovery mechanisms such as dislocation climb. The increase in ductility above the BDTT is therefore attributed to the climb of the 001 line type dislocations which in combination with dislocation glide enable grain boundary compatibility to be maintained at the higher temperatures.

Pediatric living donor liver transplantation for congenital hepatic fibrosis using a mother's graft with von Meyenburg complex: A case report.

PubMed

Yamada, Naoya; Sanada, Yukihiro; Katano, Takumi; Tashiro, Masahisa; Hirata, Yuta; Okada, Noriki; Ihara, Yoshiyuki; Miki, Atsushi; Sasanuma, Hideki; Urahashi, Taizen; Sakuma, Yasunaru; Mizuta, Koichi

2016-11-28

This is the first report of living donor liver transplantation (LDLT) for congenital hepatic fibrosis (CHF) using a mother's graft with von Meyenburg complex. A 6-year-old girl with CHF, who suffered from recurrent gastrointestinal bleeding, was referred to our hospital for liver transplantation. Her 38-year-old mother was investigated as a living donor and multiple biliary hamartoma were seen on her computed tomography and magnetic resonance imaging scan. The mother's liver function tests were normal and she did not have any organ abnormality, including polycystic kidney disease. LDLT using the left lateral segment (LLS) graft from the donor was performed. The donor LLS graft weighed 250 g; the graft recipient weight ratio was 1.19%. The operation and post-operative course of the donor were uneventful and she was discharged on post-operative day (POD) 8. The graft liver function was good, and the recipient was discharged on POD 31. LDLT using a graft with von Meyenburg complex is safe and useful. Long-term follow-up is needed with respect to graft liver function and screening malignant tumors.

Combinations of mutant FAD2 and FAD3 genes to produce high oleic acid and low linolenic acid soybean oil.

PubMed

Pham, Anh-Tung; Shannon, J Grover; Bilyeu, Kristin D

2012-08-01

High oleic acid soybeans were produced by combining mutant FAD2-1A and FAD2-1B genes. Despite having a high oleic acid content, the linolenic acid content of these soybeans was in the range of 4-6 %, which may be high enough to cause oxidative instability of the oil. Therefore, a study was conducted to incorporate one or two mutant FAD3 genes into the high oleic acid background to further reduce the linolenic acid content. As a result, soybean lines with high oleic acid and low linolenic acid (HOLL) content were produced using different sources of mutant FAD2-1A genes. While oleic acid content of these HOLL lines was stable across two testing environments, the reduction of linolenic acid content varied depending on the number of mutant FAD3 genes combined with mutant FAD2-1 genes, on the severity of mutation in the FAD2-1A gene, and on the testing environment. Combination of two mutant FAD2-1 genes and one mutant FAD3 gene resulted in less than 2 % linolenic acid content in Portageville, Missouri (MO) while four mutant genes were needed to achieve the same linolenic acid in Columbia, MO. This study generated non-transgenic soybeans with the highest oleic acid content and lowest linolenic acid content reported to date, offering a unique alternative to produce a fatty acid profile similar to olive oil.

Deletion of the von Hippel-Lindau Gene in Hemangioblasts Causes Hemangioblastoma-like Lesions in Murine Retina.

PubMed

Wang, Herui; Shepard, Matthew J; Zhang, Chao; Dong, Lijin; Walker, Dyvon; Guedez, Liliana; Park, Stanley; Wang, Yujuan; Chen, Shida; Pang, Ying; Zhang, Qi; Gao, Chun; Wong, Wai T; Wiley, Henry; Pacak, Karel; Chew, Emily Y; Zhuang, Zhengping; Chan, Chi-Chao

2018-03-01

von Hippel-Lindau (VHL) disease is an autosomal-dominant tumor predisposition syndrome characterized by the development of highly vascularized tumors and cysts. LOH of the VHL gene results in aberrant upregulation of hypoxia-inducible factors (HIF) and has been associated with tumor formation. Hemangioblastomas of the central nervous system and retina represent the most prevalent VHL-associated tumors, but no VHL animal model has reproduced retinal capillary hemangioblastomas (RCH), the hallmark lesion of ocular VHL. Here we report our work in developing a murine model of VHL-associated RCH by conditionally inactivating Vhl in a hemangioblast population using a Scl -Cre-ERT2 transgenic mouse line. In transgenic mice carrying the conditional allele and the Scl -Cre-ERT2 allele, 64% exhibited various retinal vascular anomalies following tamoxifen induction. Affected Vhl -mutant mice demonstrated retinal vascular lesions associated with prominent vasculature, anomalous capillary networks, hemorrhage, exudates, and localized fibrosis. Histologic analyses showed RCH-like lesions characterized by tortuous, dilated vasculature surrounded by "tumorlet" cell cluster and isolated foamy stromal cells, which are typically associated with RCH. Fluorescein angiography suggested increased vascular permeability of the irregular retinal vasculature and hemangioblastoma-like lesions. Vhl deletion was detected in "tumorlet" cells via microdissection. Our findings provide a phenotypic recapitulation of VHL-associated RCH in a murine model that may be useful to study RCH pathogenesis and therapeutics aimed at treating ocular VHL. Significance: This study describes a model that phenotypically recapitulates a form of retinal pathogenesis that is driven by genetic loss of the VHL tumor suppressor, providing a useful tool for its study and therapeutic intervention. Cancer Res; 78(5); 1266-74. ©2018 AACR . ©2018 American Association for Cancer Research.

Structural Basis for Modulation of Quality Control Fate in a Marginally Stable Protein.

PubMed

Brock, Kelly P; Abraham, Ayelet-chen; Amen, Triana; Kaganovich, Daniel; England, Jeremy L

2015-07-07

The human von Hippel-Lindau (VHL) tumor suppressor is a marginally stable protein previously used as a model substrate of eukaryotic refolding and degradation pathways. When expressed in the absence of its cofactors, VHL cannot fold and is quickly degraded by the quality control machinery of the cell. We combined computational methods with in vivo experiments to examine the basis of the misfolding propensity of VHL. By expressing a set of randomly mutated VHL sequences in yeast, we discovered a more stable mutant form. Subsequent modeling suggested the mutation had caused a conformational change affecting cofactor and chaperone interaction, and this hypothesis was then confirmed by additional knockout and overexpression experiments targeting a yeast cofactor homolog. These findings offer a detailed structural basis for the modulation of quality control fate in a model misfolded protein and highlight burial mode modeling as a rapid means to detect functionally important conformational changes in marginally stable globular domains. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Stress distribution in maxillary first molar periodontium using straight pull headgear with vertical and horizontal tubes: A finite element analysis

PubMed Central

Feizbakhsh, Masood; Kadkhodaei, Mahmoud; Zandian, Dana; Hosseinpour, Zahra

2017-01-01

Background: One of the most effective ways for distal movement of molars to treat Class II malocclusion is using extraoral force through a headgear device. The purpose of this study was the comparison of stress distribution in maxillary first molar periodontium using straight pull headgear in vertical and horizontal tubes through finite element method. Materials and Methods: Based on the real geometry model, a basic model of the first molar and maxillary bone was obtained using three-dimensional imaging of the skull. After the geometric modeling of periodontium components through CATIA software and the definition of mechanical properties and element classification, a force of 150 g for each headgear was defined in ABAQUS software. Consequently, Von Mises and Principal stresses were evaluated. The statistical analysis was performed using T-paired and Wilcoxon nonparametric tests. Results: Extension of areas with Von Mises and Principal stresses utilizing straight pull headgear with a vertical tube was not different from that of using a horizontal tube, but the numerical value of the Von Mises stress in the vertical tube was significantly reduced (P < 0/05). On the other hand, the difference of the principal stress between both tubes was not significant (P > 0/05). Conclusion: Based on the results, when force applied to the straight pull headgear with a vertical tube, Von Mises stress was reduced significantly in comparison with the horizontal tube. Therefore, to correct the mesiolingual movement of the maxillary first molar, vertical headgear tube is recommended. PMID:28584535

Genes and Alcohol Consumption: Studies with Mutant Mice

PubMed Central

Mayfield, Jody; Arends, Michael A.; Harris, R. Adron; Blednov, Yuri A.

2017-01-01

In this chapter, we review the effects of global null mutant and overexpressing transgenic mouse lines on voluntary self-administration of alcohol. We examine approximately 200 publications pertaining to the effects of 155 mouse genes on alcohol consumption in different drinking models. The targeted genes vary in function and include neurotransmitter, ion channel, neuroimmune, and neuropeptide signaling systems. The alcohol self-administration models include operant conditioning, two- and four-bottle choice continuous and intermittent access, drinking in the dark limited access, chronic intermittent ethanol, and scheduled high alcohol consumption tests. Comparisons of different drinking models using the same mutant mice are potentially the most informative, and we will highlight those examples. More mutants have been tested for continuous two-bottle choice consumption than any other test; of the 137 mouse genes examined using this model, 97 (72%) altered drinking in at least one sex. Overall, the effects of genetic manipulations on alcohol drinking often depend on the sex of the mice, alcohol concentration and time of access, genetic background, as well as the drinking test. PMID:27055617

Power of tests of normality for detecting contaminated normal samples

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thode, H.C. Jr.; Smith, L.A.; Finch, S.J.

1981-01-01

Seventeen tests of normality or goodness of fit were evaluated for power at detecting a contaminated normal sample. This study used 1000 replications each of samples of size 12, 17, 25, 33, 50, and 100 from six different contaminated normal distributions. The kurtosis test was the most powerful over all sample sizes and contaminations. The Hogg and weighted Kolmogorov-Smirnov tests were second. The Kolmogorov-Smirnov, chi-squared, Anderson-Darling, and Cramer-von-Mises tests had very low power at detecting contaminated normal random variables. Tables of the power of the tests and the power curves of certain tests are given.

Wernher von Braun

NASA Image and Video Library

1959-01-01

Five of the seven original astronauts are seen with Dr. von Braun inspecting the Mercury-Redstone hardware in the Fabrication Laboratory of Army Ballistic Missile Agency (ABMA) in 1959. Left to right: Astronauts Walter Schirra, Alan Shepard, John Glenn, Scott Carpenter, Gordon Cooper, and Dr. von Braun.

Portrait of Dr. Von Braun with Walt Disney, 1954.

NASA Technical Reports Server (NTRS)

1954-01-01

Marshall Center Director Dr. Wernher Von Braun is pictured with Walt Disney during a visit to the Marshall Space Flight Center in 1954. In the 1950s, Dr. Von Braun while working in California on the Saturn project, also worked with Disney studios as a technical director in making three films about Space Exploration for television. Disney's tour of Marshall in 1965 was Von Braun's hope for a renewed public interest in the future of the Space Program at NASA.

Alexander von Humboldt and the concept of animal electricity.

PubMed

Kettenmann, H

1997-06-01

More than two hundred years ago, Alexander von Humboldt helped to establish Galvani's view that muscle and nerve tissue are electrically excitable. His 1797 publication was a landmark for establishing the concept of animal electricity. Almost half a century later, von Humboldt became the mentor of the young du Bois-Reymond. With the help of von Humboldt's promotion, du Bois-Reymond demonstrated convincingly that animal tissue has the intrinsic capacity to generate electrical activity, and thus laid the ground for modern electrophysiology.

Von Neumann's impossibility proof: Mathematics in the service of rhetorics

NASA Astrophysics Data System (ADS)

Dieks, Dennis

2017-11-01

According to what has become a standard history of quantum mechanics, in 1932 von Neumann persuaded the physics community that hidden variables are impossible as a matter of principle, after which leading proponents of the Copenhagen interpretation put the situation to good use by arguing that the completeness of quantum mechanics was undeniable. This state of affairs lasted, so the story continues, until Bell in 1966 exposed von Neumann's proof as obviously wrong. The realization that von Neumann's proof was fallacious then rehabilitated hidden variables and made serious foundational research possible again. It is often added in recent accounts that von Neumann's error had been spotted almost immediately by Grete Hermann, but that her discovery was of no effect due to the dominant Copenhagen Zeitgeist. We shall attempt to tell a story that is more historically accurate and less ideologically charged. Most importantly, von Neumann never claimed to have shown the impossibility of hidden variables tout court, but argued that hidden-variable theories must possess a structure that deviates fundamentally from that of quantum mechanics. Both Hermann and Bell appear to have missed this point; moreover, both raised unjustified technical objections to the proof. Von Neumann's argument was basically that hidden-variables schemes must violate the ;quantum principle; that physical quantities are to be represented by operators in a Hilbert space. As a consequence, hidden-variables schemes, though possible in principle, necessarily exhibit a certain kind of contextuality. As we shall illustrate, early reactions to Bohm's theory are in agreement with this account. Leading physicists pointed out that Bohm's theory has the strange feature that pre-existing particle properties do not generally reveal themselves in measurements, in accordance with von Neumann's result. They did not conclude that the ;impossible was done; and that von Neumann had been shown wrong.

von Willebrand's disease antigen II. A new plasma and platelet antigen deficient in severe von Willebrand's disease.

PubMed Central

Montgomery, R R; Zimmerman, T S

1978-01-01

Factor VIII-related antigen (VIIIag) is deficient in plasma and platelets of patients with severe von Willebrand's disease. This study reports a second von Willebrand's disease antigen (vWagII), distinct from VIIIag, that is also deficient in the platelets and plasma of patients with severe von Willebrand's disease. VIIIag and vWagII are separable by molecular exclusion chromatography, sucrose density gradient ultracentrifugation, and crossed immunoelectrophoresis. They show reactions of immunologic nonidentity with each other, and thus, do not share a precursor-product relationship. vWagII is released from normal platelets during blood clotting, accounting for a fourfold higher concentration of vWagII in serum over plasma. Images PMID:307007

AMANDA and D0 as a Test Environment for the LHC Computing Grid (in German)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harenberg, Torsten

2005-08-01

Die Suche nach den Grundbausteinen der Materie und nach den Kräften, die zwischen ihnen wirken, ist das Forschungsgebiet der Hochenergiephysik. Mit immer größer werdenden Teilchenbeschleunigern erreicht man immer tiefer gehende Erkenntnisse und dringt dabei in Energiebereiche vor, wie sie kurz nach dem Urknall herrschten. Im Moment ist das Tevatron am Fermilab der energ piereichste Teilchenbeschleuniger der Welt mit einer Schwerpunktsenergie von √s = 1, 96 TeV. Um die bei diesen hohen Energien entstehende Anzahl von Teilchen zu messen, sind auch immer höher auflösende Detektoren nötig. Dem wurde dadurch Rechnung getragen, dass mit der Steigerung der Schwerpunktsenergie am Tevatron auch diemore » Detektoren DØ und CDF1) teilweise erneuert wurden.« less

Dr. von Braun Standing by Five F-1 Engines

NASA Technical Reports Server (NTRS)

2004-01-01

A pioneer of America's space program, Dr. von Braun stands by the five F-1 engines of the Saturn V launch vehicle. This Saturn V vehicle is an actual test vehicle which has been displayed at the U.S. Space Rocket Center in Huntsville, Alabama. Designed and developed by Rocketdyne under the direction of the Marshall Space Flight Center, a cluster of five F-1 engines was mounted on the Saturn V S-IC (first) stage. The engines measured 19-feet tall by 12.5-feet at the nozzle exit and burned 15 tons of liquid oxygen and kerosene each second to produce 7,500,000 pounds of thrust. The S-IC stage is the first stage, or booster, of a 364-foot long rocket that ultimately took astronauts to the Moon.

Scientific Research and Oncoming Vehicles: Can Radical Constructivists Embrace One and Dodge the Other?

NASA Astrophysics Data System (ADS)

Staver, John R.

The author's purpose in this article was to respond to two questions raised by Roth and Lawson in the September, 1993, issue of the Journal of Research in Science Teaching. Question 1: Would a radical constructivist step out of the path of an approaching vehicle? Question 2: In the conduct of inquiry, would a radical constructivist employ a controlled experiment, test a hypothesis, and quantitatively analyze the data? The author answers each question affirmatively, using selected work of Heinz von Foerster, Ernst von Glasersfeld, and others in developing the answers. Issues central to the development include the nature of truth and knowledge, the concept of fit versus match, and the notion that inquiry is driven by questions, with methods as subordinate to questions.

Pilot Scale Production and Testing of a Recombinant Staphylococcal Enterotoxin (SEB) Triple Mutant

DTIC Science & Technology

2017-09-01

1 PILOT-SCALE PRODUCTION AND TESTING OF A RECOMBINANT STAPHYLOCOCCAL ENTEROTOXIN (SEB) TRIPLE MUTANT ECBC...Disclaimer The findings in this report are not to be construed as an official Department of the Army position unless so designated by other authorizing...TYPE Final 3. DATES COVERED (From - To) Mar 2010 – Dec 2011 4. TITLE AND SUBTITLE Pilot-Scale Production and Testing of a Recombinant

Imaginal Disc Abnormalities in Lethal Mutants of Drosophila

PubMed Central

Shearn, Allen; Rice, Thomas; Garen, Alan; Gehring, Walter

1971-01-01

Late lethal mutants of Drosophila melanogaster, dying after the larval stage of development, were isolated. The homozygous mutant larvae were examined for abnormal imaginal disc morphology, and the discs were injected into normal larval hosts to test their capacities to differentiate into adult structures. In about half of the mutants analyzed, disc abnormalities were found. Included among the abnormalities were missing discs, small discs incapable of differentiating, morphologically normal discs with limited capacities for differentiation, and discs with homeotic transformations. In some mutants all discs were affected, and in others only certain discs. The most extreme abnormal phenotype is a class of “discless” mutants. The viability of these mutant larvae indicates that the discs are essential only for the development of an adult and not of a larva. The late lethals are therefore a major source of mutants for studying the genetic control of disc formation. Images PMID:5002822

New species of Anisophya Karabag from Chile (Orthoptera: Tettigoniidae: Phanopterinae)

USDA-ARS?s Scientific Manuscript database

Many of the most primitive Neotropical bush katydids (Phaneropterinae) — including species of Cosmophyllum Blanchard, Stenophylla Brunner von Wattenwyl, Marenestha Brunner von Wattenwyl, Anisophya Karabag, Coryphoda Brunner von Wattenwyl, and Burgilis Stål — are endemic in Chile. The Chilean species...

von Baer's law for the ages: lost and found principles of developmental evolution.

PubMed

Abzhanov, Arhat

2013-12-01

In 1828, Karl Ernst von Baer formulated a series of empirically defined rules, which became widely known as the 'Law of Development' or 'von Baer's law of embryology'. This was one the most significant attempts to define the principles that connected morphological complexity and embryonic development. Understanding this relation is central to both evolutionary biology and developmental genetics. Von Baer's ideas have been both a source of inspiration to generations of biologists and a target of continuous criticism over many years. With advances in multiple fields, including paleontology, cladistics, phylogenetics, genomics, and cell and developmental biology, it is now possible to examine carefully the significance of von Baer's law and its predictions. In this review, I argue that, 185 years after von Baer's law was first formulated, its main concepts after proper refurbishing remain surprisingly relevant in revealing the fundamentals of the evolution-development connection, and suggest that their explanation should become the focus of renewed research. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Trajectory of Techniques: Lessons from the Past.

ERIC Educational Resources Information Center

Crease, Robert P.

1992-01-01

Discusses role of laboratory techniques in scientific investigations. Describes Rutherford's development of scattering techniques and von Wassermann's development of test for syphilis. States that discovering an effect requires a brilliant scientist, however, making it a technique requires that it be made usable by ordinary people. Uses Moseley's…

Spitznävi: unterschiedliche klinische, dermatoskopische und histopathologische Merkmale in der Kindheit.

PubMed

Dika, Emi; Neri, Iria; Fanti, Pier Alessandro; Barisani, Alessia; Ravaioli, Giulia Maria; Patrizi, Annalisa

2017-01-01

Die Charakterisierung der klinischen Merkmale und des biologischen Potenzials von Spitznävi hat in den letzten Jahrzehnten breites Interesse gefunden. Das Ziel dieser Arbeit ist die Beschreibung der klinischen und dermatoskopischen Merkmale von Spitznävi sowie des klinischen Ergebnisses nach chirurgischer Exzision von Spitznävi in drei pädiatrischen Altersgruppen. Restrospektive Studie zur Analyse von klinischen Merkmalen, videodermatoskopischen Bildern, histopathologischen Diagnosen und Behandlungsergebnissen. Der Grad der Pigmentierung wurde sowohl klinisch als auch histopathologisch beurteilt. Bei 71 Patienten wurden 72 spitzoide Neoplasien entfernt. Videodermatologische Bilder lagen für 41 Patienten vor. Das Muster der Pigmentierung korrelierte signifikant mit dem Alter der Patienten: Hyperpigmentierte Läsionen waren bei Vorschulkindern selten, bei Patienten von 7 bis 12 Jahren und ab 13 Jahren dagegen häufiger. Eine histopathologische Diagnose von atypischen Spitznävi wurde selten durchgeführt. Keiner der Patienten, bei denen ursprünglich ein atypischer Spitznävus diagnostiziert worden war, entwickelte ein Lokalrezidiv oder Metastasen während der anschließenden Nachbeobachtung. Pigmentierte Spitznävi traten im Alter ab 13 Jahren häufiger auf. Die Studie bestätigt andere Berichte über die Altersverteilung von Pigmentierungsmustern und hebt die geringe Anzahl atypischer Spitznävi bei pädiatrischen Patienten hervor sowie das Ausbleiben von Rezidiven bei der langfristigen Nachbeobachtung. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Hazardous Waste Cleanup: Von Roll Isola USA Incorporated in Schenectady, New York

EPA Pesticide Factsheets

The Riverview facility is a 52-acre manufacturing facility located on Von Roll Drive in Schenectady, New York. The facility is owned and operated by Von Roll Isola USA, Inc., and produces solid and liquid insulating materials and tapes for the electrical

Dr. von Braun Tries Out the Neutral Buoyancy Simulator (NBS)

NASA Technical Reports Server (NTRS)

1967-01-01

Marshall Space Flight Center (MSFC) Director, Dr. von Braun, submerges after spending some time under water in the MSFC Neutral Buoyancy Simulator (NBS). Weighted to a neutrally buoyant condition, Dr. von Braun was able to perform tasks underwater which simulated weightless conditions found in space.

["Nicolaus Ficke... who practiced physiognomy, astrology, etc. was also a bad man"].

PubMed

Lenke, Nils; Roudet, Nicolas

2012-01-01

This arcticle summarizes what could be learned from newly discovered documents about the biography of Nicolas von Vicken, first known reader of Kepler's "Astronomia Nova" and Kepler's partner in an exchange of more than a dozen letters over several years. Von Vicken stems from a rich and influential family of merchants in Riga, made noble by the Polish King (who ruled Riga at the time) in 1580. His education included legal studies at the universities of Königsberg, Leipzig and Rostock, partially overlapping with a stay of ten years at the Polish court. There von Vicken pursued family business but also served in an official court role. In 1600/1 von Vicken switched sides and started to serve the Swedish ruler (and later king) Duke Carl IX, who was at war with Poland to gain control over Riga and Livonia. In 1602 a mission for Sweden to Northern Germany brought him in conflict with Francis II, Duke of Saxe-Lauenburg, who accused von Vicken of withholding money from him, which was supposed to be used for hiring troops. Von Vicken, together with his brother Heinrich, was imprisoned, but could flee. During a mission to Maximilian III, Archduke of Austria, in 1599/1600 von Vicken had been initiated as an alchemist and astrologer through reading the works of Paracelsus and his future stations in life were influenced by this. These include an attempt to get employed at the Saxon court in Dresden, and stays in Wolfenbiittel and Halberstadt, both ruled by Duke Henry Julius of Brunswick-Lüneburg. Von Vicken offered various astrological and alchemical services to the Duke and private investors. With one of them he got into a serious conflict over the alleged non-fillment of a contract to produce steel in an alchemical way. During that von Vicken got imprisoned twice, in 1609 and between 1611 and 1614. A subsequent attempt to get employed by Ernst of Schaumburg left us with several letters that detail von Vicken's alchemical and astrological thinking, two of these are published here in the appendix. Since 1603 von Vicken was also in the service of Emperor Rudolf II; again he got imprisoned in Prague at least once. An interesting speculation based on some hints in the documents is that after reading Paracelsus and during his time in Leipzig von Vicken authored a book on mining, that was later to become part of the works of the alleged medevial monk Basilius Valentinus.

Design and Testing of an H2/O2 Predetonator for a Simulated Rotating Detonation Engine Channel

DTIC Science & Technology

2013-03-01

Diameter PDE Pulse Detonation Engines RDE Rotating Detonation Engine WPAFB Wright Patterson Air Force Base ZND Zeldovich, von Neumann and Doring xv...DESIGN AND TESTING OF AN H2/O2 PREDETONATOR FOR A SIMULATED ROTATING DETONATION ENGINE CHANNEL THESIS Stephen J. Miller, 2Lt, USAF AFIT-ENY-13-M-23...RELEASE; DISTRIBUTION UNLIMITED AFIT-ENY-13-M-23 DESIGN AND TESTING OF AN H2/O2 PREDETONATOR FOR A SIMULATED ROTATING DETONATION ENGINE CHANNEL Stephen

Dr. von Braun With Five of the Original Astronauts

NASA Technical Reports Server (NTRS)

1959-01-01

Five of the seven original astronauts are seen with Dr. von Braun inspecting the Mercury-Redstone hardware in the Fabrication Laboratory of Army Ballistic Missile Agency (ABMA) in 1959. Left to right: Astronauts Walter Schirra, Alan Shepard, John Glenn, Scott Carpenter, Gordon Cooper, and Dr. von Braun.

Dr. von Braun Tries Out the NBS

NASA Technical Reports Server (NTRS)

1967-01-01

Marshall Space Flight Center (MSFC) Director, Dr. von Braun, is shown fitted with suit and diving equipment as he prepares for a tryout in the MSFC Neutral Buoyancy Simulator (NBS). Weighted to a neutrally buoyant condition, Dr. von Braun was able to perform tasks underwater which simulated weightless conditions found in space.

Netz ohne doppelten Boden: Internet-Sicherheit

NASA Astrophysics Data System (ADS)

Fichtner, Johann

2002-07-01

Die Sicherheitslücken des heutigen Internets haben zwei Ursachen: sein ursprüngliches Design für rein militärische Zwecke sowie die gefährliche Sorglosigkeit der Entwickler und Betreiber von Internet-Komponenten. Dabei kann ein kleiner Kreis von Experten Angriffe auf die eigentlichen Netzknoten ausführen. Typische Hacker-Angriffe kommen von Endsystemen des Internets und richten sich auch gegen Endsysteme wie Firmen-Intranets oder einzelne PCs. Dagegen gibt es eine Reihe von Schutzmöglichkeiten. Es ist jedoch keine einfache Lösung zur Erhöhung der Internet-Sicherheit in Sicht.

[Albert Reder Ritter von Schellmann (1826-1904)].

PubMed

Schmidt, G; Holubar, K

1990-01-01

Albert Reder von Schellmann (1826-1904) was an important syphilidologist of the Vienna Medical School in the second half of the nineteenth century. He went in for the dualistic concept of the origin of syphilis and ulcer caused by soft chancre. In 1870 - Reder became head of a third dermato-syphilidologic department in the "Josephinum" in Vienna, where military surgeons got their medical education. At the same time the two full professorships of dermatosyphilidology in the Vienna General Hospital were held by Ferdinand von Hebra (1816-1880) and Carl Ludwig Sigmund von Ilanor (1810-1883).

Einsatz molekularer Methoden für Starterkulturen

NASA Astrophysics Data System (ADS)

Ehrmann, Matthias A.; Pavlovic, Melanie

Unter Starterkulturen versteht man Mikroorganismen (Bakterien, Hefen, Pilze), die pflanzlichen bzw. tierischen Rohstoffen zur gezielten Veränderung ihrer chemischen Zusammensetzung zugesetzt werden. Sie dienen im Wesentlichen der Aromabildung, der Strukturveränderung und der Konservierung der Lebensmittel und werden aufgrund spezieller, funktioneller Eigenschaften selektiert. Die Zugabe von Starterkulturen erfolgt in der Regel in relativ hohen Keimzahlen in Form von Rein- oder Mischkulturen. Die zum Einsatz kommenden Mikroorganismen sind ebenso zahlreich wie die daraus resultierenden Produkte und reichen von der Fermentation von Milchprodukten, Fleisch und Gemüse durch Milchsäurebakterien über die Essigsäureherstellung bis hin zum Einsatz von Hefen in der Brau- und Weinindustrie. Hieraus ergibt sich auch eine zunehmende Bedeutung schneller und zuverlässiger Methoden zur taxonomischen Identifizierung, aber auch zur Charakterisierung des genetischen Potenzials der jeweiligen Starterkulturen.

Vortex wakes of a flapping foil in a flowing soap film

NASA Astrophysics Data System (ADS)

Schnipper, Teis; Andersen, Anders; Bohr, Tomas

2008-11-01

We present an experimental study of an oscillating, symmetric foil in a vertically flowing soap film. By varying frequency and amplitude of the oscillation we explore and visualize a variety of wake structures, including von Kármán wake, reverse von Kármán wake, 2P wake, and 2P+2S wake. We characterize the transition from the von Kármán wake (drag) to the reverse von Kármán wake (thrust) and discuss the results in relation to fish swimming. We visualize the time evolution of the vortex shedding in detail, identify the origins of the vortices comprising the wake, and propose a simple model to account for the transition from von Kármán like wakes to more exotic wake structures.

The Phenotype performance of M3 red rice mutant (Oryza sativa L.)

NASA Astrophysics Data System (ADS)

Kasim, N.; Sjahril, R.; Riadi, M.; Arbie, F.

2018-05-01

Local rice genotype generally has colour, flavour and scent more preferred by consumers, yet unfortunately it has long-lived planting period and low production. Therefore, the plant breeding practices in rice needs to be implemented for better rice varieties which are superior in terms of both quality and quantity. Our findings describe the growth character performance and the production of red rice mutant from M3 generation. This study was conducted in the Agriculture Faculty wetlands, Hasanuddin University, Makassar, by using ANOVA test with some red rice mutant genotypes i.e. 7 genotypes mutants (G1, G2, G3, G4, G5, G6 and G7) and controls/parent-plants (not the mutant). Results show that there were difference in growth performance and production of red rice mutant. Each parameter observed on each genotype had different results. Mutants produced best response in tillers production were G4 mutant with the tillers grain weight at 99.2 g, whereas by the results of the analysis of rank, mutants showed the best overall response were found in G6 mutants.

Fibroblast growth factor-10 signals development of von Brunn's nests in the exstrophic bladder

PubMed Central

Eastman, Rocky; Leaf, Elizabeth M.; Zhang, Dianzhong; True, Lawrence D.; Sweet, Robert M.; Seidel, Kristy; Siebert, Joseph R.; Grady, Richard; Mitchell, Michael E.

2010-01-01

von Brunn's nests have long been recognized as precursors of benign lesions of the urinary bladder mucosa. We report here that von Brunn's nests are especially prevalent in the exstrophic bladder, a birth defect that predisposes the patient to formation of bladder cancer. Cells of von Brunn's nest were found to coalesce into a stratified, polarized epithelium which surrounds itself with a capsule-like structure rich in types I, III, and IV collagen. Histocytochemical analysis and keratin profiling demonstrated that nested cells exhibited a phenotype similar, but not identical, to that of urothelial cells of transitional epithelium. Immunostaining and in situ hybridization analysis of exstrophic tissue demonstrated that the FGF-10 receptor is synthesized and retained by cells of von Brunn's nest. In contrast, FGF-10 is synthesized and secreted by mesenchymal fibroblasts via a paracrine pathway that targets basal epithelial cells of von Brunn's nests. Small clusters of 10pRp cells, positive for both FGF-10 and its receptor, were observed both proximal to and inside blood vessels in the lamina propria. The collective evidence points to a mechanism where von Brunn's nests develop under the control of the FGF-10 signal transduction system and suggests that 10pRp cells may be the original source of nested cells. PMID:20719973

Determination quercetin content, antioxidant and antimicrobial activity of genotype mutant Samosir shallots irradiated by gamma rays

NASA Astrophysics Data System (ADS)

Sinuraya, M.; Hanafiah, D. S.; Romulo, A.; Barus, A.

2018-02-01

The aim of the research was to study the variation in antioxidant and antimicrobial activity as well as the total quercetin content of the fifth generation genotypes mutant Samosir shallot irradiated by gamma rays. The studies conducted included the assessment of quercetin content, antioxidant and antimicrobial activity in shallot bulbs after long-term storage (6 months in the room temperature). Quercetin content of 20 selected genotype mutants of irradiated shallot bulbs along with untreated populations were calculated using quercetin (QU) as a standard. Antioxidant activities of 8 genotype mutant were determined using DPPH. Antimicrobial activity of bulb extracts were tested against six bacteria including Staphylococcus aurous, Enterococcus faecalis, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae and oneyeastCandida albicans. The results showed that population of genotype mutants irradiated with dosage 2Gy, 4 Gy, 5 Gy and 6 Gy have higher quercetin content than control samples. None of the genotype mutants exhibited antibacterial inhibitory against all microorganism tested except for the sample number 2 and 6 (bulbs generated from the plants irradiated by gamma rays with dosage at 2 Gy and 6 Gy). There was also none of the genotypes observed exhibited significant antioxidant efficacy.

Locally Compact Quantum Groups. A von Neumann Algebra Approach

NASA Astrophysics Data System (ADS)

Van Daele, Alfons

2014-08-01

In this paper, we give an alternative approach to the theory of locally compact quantum groups, as developed by Kustermans and Vaes. We start with a von Neumann algebra and a comultiplication on this von Neumann algebra. We assume that there exist faithful left and right Haar weights. Then we develop the theory within this von Neumann algebra setting. In [Math. Scand. 92 (2003), 68-92] locally compact quantum groups are also studied in the von Neumann algebraic context. This approach is independent of the original C^*-algebraic approach in the sense that the earlier results are not used. However, this paper is not really independent because for many proofs, the reader is referred to the original paper where the C^*-version is developed. In this paper, we give a completely self-contained approach. Moreover, at various points, we do things differently. We have a different treatment of the antipode. It is similar to the original treatment in [Ann. Sci. & #201;cole Norm. Sup. (4) 33 (2000), 837-934]. But together with the fact that we work in the von Neumann algebra framework, it allows us to use an idea from [Rev. Roumaine Math. Pures Appl. 21 (1976), 1411-1449] to obtain the uniqueness of the Haar weights in an early stage. We take advantage of this fact when deriving the other main results in the theory. We also give a slightly different approach to duality. Finally, we collect, in a systematic way, several important formulas. In an appendix, we indicate very briefly how the C^*-approach and the von Neumann algebra approach eventually yield the same objects. The passage from the von Neumann algebra setting to the C^*-algebra setting is more or less standard. For the other direction, we use a new method. It is based on the observation that the Haar weights on the C^*-algebra extend to weights on the double dual with central support and that all these supports are the same. Of course, we get the von Neumann algebra by cutting down the double dual with this unique support projection in the center. All together, we see that there are many advantages when we develop the theory of locally compact quantum groups in the von Neumann algebra framework, rather than in the C^*-algebra framework. It is not only simpler, the theory of weights on von Neumann algebras is better known and one needs very little to go from the C^*-algebras to the von Neumann algebras. Moreover, in many cases when constructing examples, the von Neumann algebra with the coproduct is constructed from the very beginning and the Haar weights are constructed as weights on this von Neumann algebra (using left Hilbert algebra theory). This paper is written in a concise way. In many cases, only indications for the proofs of the results are given. This information should be enough to see that these results are correct. We will give more details in forthcoming paper, which will be expository, aimed at non-specialists. See also [Bull. Kerala Math. Assoc. (2005), 153-177] for an 'expanded' version of the appendix.

ENU-mutagenesis mice with a non-synonymous mutation in Grin1 exhibit abnormal anxiety-like behaviors, impaired fear memory, and decreased acoustic startle response

PubMed Central

2013-01-01

Background The Grin1 (glutamate receptor, ionotropic, NMDA1) gene expresses a subunit of N-methyl-D-aspartate (NMDA) receptors that is considered to play an important role in excitatory neurotransmission, synaptic plasticity, and brain development. Grin1 is a candidate susceptibility gene for neuropsychiatric disorders, including schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder (ADHD). In our previous study, we examined an N-ethyl-N-nitrosourea (ENU)-generated mutant mouse strain (Grin1Rgsc174/Grin1+) that has a non-synonymous mutation in Grin1. These mutant mice showed hyperactivity, increased novelty-seeking to objects, and abnormal social interactions. Therefore, Grin1Rgsc174/Grin1+ mice may serve as a potential animal model of neuropsychiatric disorders. However, other behavioral characteristics related to these disorders, such as working memory function and sensorimotor gating, have not been fully explored in these mutant mice. In this study, to further investigate the behavioral phenotypes of Grin1Rgsc174/Grin1+ mice, we subjected them to a comprehensive battery of behavioral tests. Results There was no significant difference in nociception between Grin1Rgsc174/Grin1+ and wild-type mice. The mutants did not display any abnormalities in the Porsolt forced swim and tail suspension tests. We confirmed the previous observations that the locomotor activity of these mutant mice increased in the open field and home cage activity tests. They displayed abnormal anxiety-like behaviors in the light/dark transition and the elevated plus maze tests. Both contextual and cued fear memory were severely deficient in the fear conditioning test. The mutant mice exhibited slightly impaired working memory in the eight-arm radial maze test. The startle amplitude was markedly decreased in Grin1Rgsc174/Grin1+ mice, whereas no significant differences between genotypes were detected in the prepulse inhibition (PPI) test. The mutant mice showed no obvious deficits in social behaviors in three different social interaction tests. Conclusions This study demonstrated that the Grin1Rgsc174/Grin1+ mutation causes abnormal anxiety-like behaviors, a deficiency in fear memory, and a decreased startle amplitude in mice. Although Grin1Rgsc174/Grin1+ mice only partially recapitulate symptoms of patients with ADHD, schizophrenia, and bipolar disorder, they may serve as a unique animal model of a certain subpopulation of patients with these disorders. PMID:23688147

Analyse der pharmazeutischen Versorgungssituation von Patienten mit Psoriasis-Arthritis auf Basis von Routinedaten der Gesetzlichen Krankenversicherung.

PubMed

Sondermann, Wiebke; Ventzke, Julia; Matusiewicz, David; Körber, Andreas

2018-03-01

Die Psoriasis-Arthritis (PsA) gehört zu den chronisch entzündlichen Gelenkerkrankungen. Trotz zahlreicher versorgungswissenschaftlicher Studien in Deutschland liegen zur pharmazeutischen Versorgungssituation von PsA-Patienten bisher kaum aktuelle Ergebnisse vor. Mit Hilfe einer systematischen Literaturrecherche sowie anhand von Routinedaten der Allgemeinen Ortskrankenkasse (AOK) Rheinland/Hamburg wird ein aktueller Überblick über die pharmazeutische Versorgung von PsA-Patienten in Deutschland gegeben. Selektiert wurden Versicherte aus dem ambulanten und stationären Bereich, die im 1. und 2. Quartal des Jahres 2014 die gesicherte Abrechnungsdiagnose Psoriasis-Arthritis L40.5+ aufwiesen. Anschließend wurden auf Basis dieser "vorab definierten" Kohorte die Arzneimitteldaten für 5 Jahre (01.01.2010-31.12.2014) abgerufen. Es konnten insgesamt n  =  3205 Versicherte (45 % männlich, 55 % weiblich) der AOK Rheinland/Hamburg mit einer gesicherten PsA-Diagnose selektiert werden. Das Durchschnittsalter betrug 58,9 Jahre. 53,7 % der PsA-Patienten wurden mit systemischen PsA-relevanten Arzneimitteln versorgt. Nichtsteroidale Antirheumatika (NSAR) wurden am häufigsten verordnet, gefolgt von systemischen Glucocorticoiden. Von den selektierten PsA-Patienten, die eine Systemtherapie erhielten, wurden 72,1 % mittels einer Disease-modifying-antirheumatic-Drug (DMARD)-Monotherapie behandelt, gefolgt von der Kombinationstherapie aus DMARDs und Biologika (20,9 %). Die pharmakologische Therapie der PsA muss eine Gewährleistung zwischen adäquater Versorgung der PsA mit Verhinderung der Krankheitsprogression und ökonomischer Verantwortung darstellen. © 2018 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Developmentally arrested structures preceding cerebellar tumors in von Hippel–Lindau disease

PubMed Central

Shively, Sharon B; Falke, Eric A; Li, Jie; Tran, Maxine G B; Thompson, Eli R; Maxwell, Patrick H; Roessler, Erich; Oldfield, Edward H; Lonser, Russell R; Vortmeyer, Alexander O

2011-01-01

There is increasing evidence that suggests that knockout of tumor-suppressor gene function causes developmental arrest and protraction of cellular differentiation. In the peripheral nervous system of patients with the tumor-suppressor gene disorder, von Hippel–Lindau disease, we have demonstrated developmentally arrested structural elements composed of hemangioblast progenitor cells. Some developmentally arrested structural elements progress to a frank tumor, hemangioblastoma. However, in von Hippel–Lindau disease, hemangioblastomas are frequently observed in the cerebellum, suggesting an origin in the central nervous system. We performed a structural and topographic analysis of cerebellar tissues obtained from von Hippel–Lindau disease patients to identify and characterize developmentally arrested structural elements in the central nervous system. We examined the entire cerebella of five tumor-free von Hippel–Lindau disease patients and of three non-von Hippel–Lindau disease controls. In all, 9 cerebellar developmentally arrested structural elements were detected and topographically mapped in 385 blocks of von Hippel–Lindau disease cerebella. No developmentally arrested structural elements were seen in 214 blocks from control cerebella. Developmentally arrested structural elements are composed of poorly differentiated cells that express hypoxia-inducible factor (HIF)2α, but not HIF1α or brachyury, and preferentially involve the molecular layer of the dorsum cerebelli. For the first time, we identify and characterize developmentally arrested structural elements in the central nervous system of von Hippel–Lindau patients. We provide evidence that developmentally arrested structural elements in the cerebellum are composed of developmentally arrested hemangioblast progenitor cells in the molecular layer of the dorsum cerebelli. PMID:21499240

Microinjection of cytoplasm as a test of complementation in Paramecium

PubMed Central

1982-01-01

Mutants in Paramecium tetraurelia, unable to generate action potentials, have been isolated as cells which show no backward swimming in response to ionic stimulation. These "pawn" mutants belong to at least three complementation groups designated pwA, pwB, and pwC. We have found that microinjection of cytoplasm from a wild-type donor into a pawn recipient of any of the three complementation groups restores the ability of the pawn to generate action potentials and hence swim backward. In addition, the cytoplasm from a pawn cannot restore a recipient of the same complementation group, but that from a pawn of a different group can. Electrophysiological analysis had demonstrated that the restoration of backward swimming is not due to a simple addition of ions but represents a profound change in the excitable membrane of the recipient pawn cells. Using known pawn mutants and those which had previously been unclassified, we have been able to establish a perfect concordance of genetic complementation and complementation by cytoplasmic transfer through microinjection. This method has been used to classify pawn mutants that are sterile or hard- to-mate and to examine the ability of cytoplasms from different species of ciliated protozoa to restore the ability to swim backward in the pawn mutants of P. tetraurelia. A cell homogenate has also been fractionated by centrifugation to further purify the active components. These results demonstrate that transfer of cytoplasm between cells by microinjection can be a valid and systematic method to classify mutants. This test is simpler to perform than the genetic complementation test and can be used under favorable conditions in mutants that are sterile and in cells of different species. PMID:7061597

Modal Testing of the NPSAT1 Engineering Development Unit

DTIC Science & Technology

2012-07-01

erkläre ich, dass die vorliegende Master Arbeit von mir selbstständig und nur unter Verwendung der angegebenen Quellen und Hilfsmittel angefertigt...logarithmic scale . As 5 Figure 2 shows, natural frequencies are indicated by large values of the first CMIF (peaks), and multiple modes can be detected by...structure’s behavior. Ewins even states, “that no large- scale modal test should be permitted to proceed until some preliminary SDOF analyses have

Dr. von Braun with Seven Original Mercury Astronauts

NASA Technical Reports Server (NTRS)

1959-01-01

In this photo, Dr. Wernher von Braun, Director of the U.S. Army Ballistic Missile Agency's (ABMA) Development Operations Division, is shown briefing the seven original Mercury astronauts in ABMA's Fabrication Laboratory. (Left to right) Guss Grissom, Walter Schirra, Alan Shepard, John Glenn, Scott Carpenter, Gordon Cooper, Donald Slayton, and Dr. von Braun.

Von Neumann was not a Quantum Bayesian.

PubMed

Stacey, Blake C

2016-05-28

Wikipedia has claimed for over 3 years now that John von Neumann was the 'first quantum Bayesian'. In context, this reads as stating that von Neumann inaugurated QBism, the approach to quantum theory promoted by Fuchs, Mermin and Schack. This essay explores how such a claim is, historically speaking, unsupported. © 2016 The Author(s).

Dr. von Braun Tries Out the Neutral Buoyancy Simulator (NBS)

NASA Technical Reports Server (NTRS)

1967-01-01

Marshall Space Flight Center (MSFC) Director, Dr. von Braun, is shown leaving the suiting-up van wearing a pressure suit prepared for a tryout in the MSFC Neutral Buoyancy Simulator (NBS). Weighted to a neutrally buoyant condition, Dr. von Braun was able to perform tasks underwater which simulated weightless conditions found in space.

Wernher von Braun

NASA Image and Video Library

1968-01-22

Dr. Wernher Von Braun, stands in front of a Saturn IB Launch Vehicle at Kennedy Space Center (KSC). Dr. Von Braun was Marshall's first Center Director (1960-1970). Under his leadership Marshall was responsible for the development of the Saturn rockets, the Skylab project and getting the United States into Space and landing on the moon with the Apollo missions.

Von Bertalanffy's dynamics under a polynomial correction: Allee effect and big bang bifurcation

NASA Astrophysics Data System (ADS)

Leonel Rocha, J.; Taha, A. K.; Fournier-Prunaret, D.

2016-02-01

In this work we consider new one-dimensional populational discrete dynamical systems in which the growth of the population is described by a family of von Bertalanffy's functions, as a dynamical approach to von Bertalanffy's growth equation. The purpose of introducing Allee effect in those models is satisfied under a correction factor of polynomial type. We study classes of von Bertalanffy's functions with different types of Allee effect: strong and weak Allee's functions. Dependent on the variation of four parameters, von Bertalanffy's functions also includes another class of important functions: functions with no Allee effect. The complex bifurcation structures of these von Bertalanffy's functions is investigated in detail. We verified that this family of functions has particular bifurcation structures: the big bang bifurcation of the so-called “box-within-a-box” type. The big bang bifurcation is associated to the asymptotic weight or carrying capacity. This work is a contribution to the study of the big bang bifurcation analysis for continuous maps and their relationship with explosion birth and extinction phenomena.

Selective advantage of resistant strains at trace levels of antibiotics: a simple and ultrasensitive color test for detection of antibiotics and genotoxic agents.

PubMed

Liu, Anne; Fong, Amie; Becket, Elinne; Yuan, Jessica; Tamae, Cindy; Medrano, Leah; Maiz, Maria; Wahba, Christine; Lee, Catherine; Lee, Kim; Tran, Katherine P; Yang, Hanjing; Hoffman, Robert M; Salih, Anya; Miller, Jeffrey H

2011-03-01

Many studies have examined the evolution of bacterial mutants that are resistant to specific antibiotics, and many of these focus on concentrations at and above the MIC. Here we ask for the minimum concentration at which existing resistant mutants can outgrow sensitive wild-type strains in competition experiments at antibiotic levels significantly below the MIC, and we define a minimum selective concentration (MSC) in Escherichia coli for two antibiotics, which is near 1/5 of the MIC for ciprofloxacin and 1/20 of the MIC for tetracycline. Because of the prevalence of resistant mutants already in the human microbiome, allowable levels of antibiotics to which we are exposed should be below the MSC. Since this concentration often corresponds to low or trace levels of antibiotics, it is helpful to have simple tests to detect such trace levels. We describe a simple ultrasensitive test for detecting the presence of antibiotics and genotoxic agents. The test is based on the use of chromogenic proteins as color markers and the use of single and multiple mutants of Escherichia coli that have greatly increased sensitivity to either a wide range of antibiotics or specific antibiotics, antibiotic families, and genotoxic agents. This test can detect ciprofloxacin at 1/75 of the MIC.

Wind tunnel tests of Space Shuttle external tank insulation material in the aerothermal tunnel at elevated (1440 deg F) total temperatures

NASA Technical Reports Server (NTRS)

Hartman, A. S.; Nutt, K. W.

1982-01-01

Tests of the space shuttle external tank foam insulation were conducted in the von Karman Gas Dynamics Facility Tunnel C. For these tests, Tunnel C was run at Mach 4 with a total temperature of 1440 F and a total pressure which varied from 30-100 psia. Cold wall heating rates were changed by varying the test article support wedge angle and by adding and removing a shock generator or a cylindrical protuberance. Selected results are presented to illustrate the test techniques and typical data obtained.

Windkraftanlagen

NASA Astrophysics Data System (ADS)

Surek, Dominik

Windturbinenanlagen nutzen die kinetische Energie des Windes bei Geschwindigkeiten von c=4 m/s bis 25 m/s in Nabenhöhe des Windrades zur Stromerzeugung. Die oben genannten Windgeschwindigkeiten liegen im Grenzschichtbereich der ebenen Strömung (Abb. 67.1), die bei Höhen von h=100 m bis 1000 m liegen und in Großstädten mit Skylines bis 2000 m. Die größten Windturbinentürme erreichen gegenwärtig Nabenhöhen von h=160 m und Windraddurchmesser von d=130 m, d. h. mit Flügellängen von L=65 m. Die Windturbinen werden vorrangig mit 3 Schaufeln ausgeführt. Windturbinen mit einer und zwei Schaufeln waren Versuchsgeräte. Die Drehzahl von Windturbinen für Leistungen von P_{T}=2 MW betragen n=12 bis 20 min{}^{-1}. Das Windrad entzieht dem Wind mit der Anströmgeschwindigkeit c 1 nach Betz die Geschwindigkeitsdifferenz c2=(2/3) c1. Der Rest der Windgeschwindigkeit wird für die Abströmung des Windes im Leebereich c3=c1/3 benötigt. Durch den Entzug der Geschwindigkeit im Laufrad bläht sich der Abströmdurchmesser auf d3> d1 auf, der bei der Installation von Windturbinen zu beachten ist (Abb. 67.2) [Gasch und Twele(2013)]. Um die Windturbinen bei starkem Wind von c {}1> 25 m/s zu schützen, werden die Laufschaufeln durch Pitch- oder Stall-Anlagen aus dem Wind gedreht, so dass die Strömung an den Schaufeln abreißt und das Windrad in die Ruhestellung gelangt. Bei der Windgeschwindigkeit c1=25 m/s bis 34 m/s wird der Windrotor abgeschaltet. Die zulässige Maximalgeschwindigkeit liegt aus Festigkeitsgründen etwa bei . Die aktive Blattverdrehung (Pitchregelung) stellt eine Blattwinkelregelung dar, wobei die Profilnase in die Anströmung gedreht wird. Sie benötigen für die Drehzahlreduzierung keine mechanische Bremse.

Von Neumann entropy in a Rashba-Dresselhaus nanodot; dynamical electronic spin-orbit entanglement

NASA Astrophysics Data System (ADS)

Safaiee, Rosa; Golshan, Mohammad Mehdi

2017-06-01

The main purpose of the present article is to report the characteristics of von Neumann entropy, thereby, the electronic hybrid entanglement, in the heterojunction of two semiconductors, with due attention to the Rashba and Dresselhaus spin-orbit interactions. To this end, we cast the von Neumann entropy in terms of spin polarization and compute its time evolution; with a vast span of applications. It is assumed that gate potentials are applied to the heterojunction, providing a two dimensional parabolic confining potential (forming an isotropic nanodot at the junction), as well as means of controlling the spin-orbit couplings. The spin degeneracy is also removed, even at electronic zero momentum, by the presence of an external magnetic field which, in turn, leads to the appearance of Landau states. We then proceed by computing the time evolution of the corresponding von Neumann entropy from a separable (spin-polarized) initial state. The von Neumann entropy, as we show, indicates that electronic hybrid entanglement does occur between spin and two-dimensional Landau levels. Our results also show that von Neumann entropy, as well as the degree of spin-orbit entanglement, periodically collapses and revives. The characteristics of such behavior; period, amplitude, etc., are shown to be determined from the controllable external agents. Moreover, it is demonstrated that the phenomenon of collapse-revivals' in the behavior of von Neumann entropy, equivalently, electronic hybrid entanglement, is accompanied by plateaus (of great importance in quantum computation schemes) whose durations are, again, controlled by the external elements. Along these lines, we also make a comparison between effects of the two spin-orbit couplings on the entanglement (von Neumann entropy) characteristics. The finer details of the electronic hybrid entanglement, which may be easily verified through spin polarization measurements, are also accreted and discussed. The novel results of the present article, with potent applications in the field of quantum information processing, provide a deeper understanding of the electronic von Neumann entropy and hybrid entanglement that occurs in two-dimensional nanodots.

Workshop on Dynamic Fracture Held at Pasadena, California on 17-18 February 1983.

DTIC Science & Technology

1983-10-01

class of materials seems to be the basis for deliberate attempts to devise (small) test geometries that lead to quai-static str fields under rapid loading...23- 22. Kalthoff, J.F., Beinert, J., and Winkler, S., "Einflu# dynamischer Effekte auf die Bestim- mung von Rioarfestzihigkeiten und auf die

Improved Medium for Selecting Nitrate-Nonutilizing (nit) Mutants of Verticillium dahliae.

PubMed

Korolev, N; Katan, T

1997-10-01

ABSTRACT Nitrate-nonutilizing (nit) mutants are commonly used to determine vegetative compatibility between isolates of Verticillium dahliae by complementation (heterokaryon) testing. These mutants emerge spontaneously as chlorate-resistant sectors growing out of partially restricted, wild-type colonies on chlorate-amended media. The commonly used chlorate media are based on minimal medium (MMC) or cornmeal agar (CMC), amended with potassium chlorate. nit mutants recovered on these media constituted 10 to 36%(on MMC) and 25 to 45%(on CMC) of the apparently resistant sectors. An improved water agar chlorate medium (WAC) is described that is more effective for selecting chlorate-resistant nit mutants. WAC medium consists of agar (2%), glucose (0.02%), and potassium chlorate (2 to 5%). On WAC, growth of most V. dahliae isolates was strongly inhibited, and 66 to 100%(average >80%) of the chlorate-resistant sectors formed were nit mutants. Most mutants were characterized as nit1, and about 6% as NitM.

A novel approach to fitting the von Bertalanffy relationship to a mixed stock of Atlantic sturgeon harvested off the New Jersey Coast

USGS Publications Warehouse

Johnson, James H.; McKenna, James E.; Dropkin, David S.; Andrews, William D.

2005-01-01

We examined the growth characteristics of 303 Atlantic sturgeon, Acipenser oxyrinchus, caught in the commercial fishery off the New Jersey coast from 1992 to 1994 (fork length range: 93–219 cm). Sections taken from the leading pectoral fin ray were used to age each sturgeon. Ages ranged from 5–26 years. Von Bertalanffy growth models for males and females fit well, but test statistics (t-test, maximum likelihood) failed to reject the null hypothesis that growth was not significantly different between sexes. Consequently, all data were pooled and the combined data gave L∞ and K estimates of 174.2 cm and 0.144, respectively. Our growth data do not fit the pattern of slower growth and increased size in more northernly latitudes for Atlantic sturgeon observed in other work. Lack of uniformity of our growth data may be due to (1) the sturgeon fishery harvesting multiple stocks having different growth rates, and (2) size limits for the commercial fishery having created a bias in estimating growth parameters.

[Hepatitis E - More than a Rare Travel-Associated Infectious Disease!

PubMed

Wedemeyer, Heiner

2017-06-01

Übertragungswege  In Deutschland infizieren sich jedes Jahr wahrscheinlich mehr als 300 000 Menschen mit dem Hepatitis-E-Virus (HEV). Die Hepatitis E ist in Mitteleuropa in der Regel eine durch den zoonotischen HEV-Genotyp-3-verursachte autochthone, d. h. lokal erworbene Infektionskrankheit. Der Verzehr von nicht ausreichend erhitztem Schweine- oder Wildfleisch ist ein Hauptrisikofaktor für HEV-Infektionen, Übertragungen des Virus durch Bluttransfusionen sind aber auch möglich. Diagnostik  Bei Immunkompetenten kann die Diagnose einer akuten Hepatitis E mit dem Nachweis von anti-HEV-IgM gestellt werden. Serologische Tests können bei Immunsupprimierten aber falsch-negativ sein, weshalb in diesen Fällen eine HEV-Infektion nur durch den direkten Nachweis des Erregers mittels PCR im Blut oder Stuhl erfolgen sollte. Natürlicher Verlauf  Eine akute Hepatitis E kann bei Patienten mit anderen chronischen Lebererkrankungen zu einem Leberversagen führen. Chronische Verläufe, definiert durch eine Virämie von mind. 3 Monaten, sind bei Organtransplantierten mit immunsuppressiver Medikation beschrieben, können aber auch bei anderen Immundefizienzen auftreten. Eine chronische Hepatitis E kann innerhalb von Monaten zu einer fortgeschrittenen Leberfibrose oder zur Zirrhose führen. Extrahepatische Manifestationen  Extrahepatische Manifestationen können während und nach einer HEV-Infektion auftreten. Insbesondere Guillain-Barré-Syndrome und die neuralgische Schulteramyotrophie sind mit einer Hepatitis E assoziiert worden. Therapie  Ribavirin hat eine antivirale Wirksamkeit gegen HEV. Bei chronischer Hepatitis E sollte die Behandlung für 3 – 6 Monate durchgeführt werden. Therapieversagen und Rückfälle nach Beendigung einer Behandlung sind möglich. Ein Impfstoff gegen HEV ist bisher nur in China zugelassen.

Comparative Study of the Mutant Prevention Concentrations of Moxifloxacin, Levofloxacin, and Gemifloxacin against Pneumococci▿ †

PubMed Central

Credito, Kim; Kosowska-Shick, Klaudia; McGhee, Pamela; Pankuch, Glenn A.; Appelbaum, Peter C.

2010-01-01

We tested the propensity of three quinolones to select for resistant Streptococcus pneumoniae mutants by determining the mutant prevention concentration (MPC) against 100 clinical strains, some of which harbored mutations in type II topoisomerases. Compared with levofloxacin and gemifloxacin, moxifloxacin had the lowest number of strains with MPCs above the susceptibility breakpoint (P < 0.001), thus representing a lower selective pressure for proliferation of resistant mutants. Only moxifloxacin gave a 50% MPC (MPC50) value (1 μg/ml) within the susceptible range. PMID:20008781

Comparative study of the mutant prevention concentrations of moxifloxacin, levofloxacin, and gemifloxacin against pneumococci.

PubMed

Credito, Kim; Kosowska-Shick, Klaudia; McGhee, Pamela; Pankuch, Glenn A; Appelbaum, Peter C

2010-02-01

We tested the propensity of three quinolones to select for resistant Streptococcus pneumoniae mutants by determining the mutant prevention concentration (MPC) against 100 clinical strains, some of which harbored mutations in type II topoisomerases. Compared with levofloxacin and gemifloxacin, moxifloxacin had the lowest number of strains with MPCs above the susceptibility breakpoint (P<0.001), thus representing a lower selective pressure for proliferation of resistant mutants. Only moxifloxacin gave a 50% MPC (MPC50) value (1 microg/ml) within the susceptible range.

Induction of diphtheria toxin-resistant mutants in human cells by ultraviolet light

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rocchi, P.; Ferreri, A.M.; Capucci, A.

1981-01-01

Stable spontaneous mutants resistant to the protein synthesis inhibitor diphtheria toxin (DT) have been selected in human cell line EUE at a very low frequency (less than 8 x 10(-6)). U.v.-induced mutation has been quantitatively measured: treatment of cells with u.v. light increased the frequencies of diphtheria toxin resistant (DTr) mutants up to 1000-fold. The maximum recovery of DTr mutants was observed after a short expression period, for all u.v. doses tested, and was followed by a decrease in mutation frequency on subsequent passages.

Induction of diphtheria toxin-resistant mutants in human cells by ultraviolet light

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rocchi, P.; Ferreri, A.M.; Capucci, A.

1981-01-01

Stable spontaneous mutants resistant to the protein synthesis inhibitor diphtheria toxin (DT) have been selected in human cell line EUE at a very low frequency (< 8 x 10/sup -6/). U.v.-induced mutation has been quantitatively measured: treatment of cells with u.v. light increased the frequencies of diphtheria toxin resistant (DTsup(r)) mutants up to 1000-fold. The maximum recovery of DTsup(r) mutants was observed after a short expression period, for all u.v. doses tested, and was followed by a decrease in mutation frequency on subsequent passages.

Correlation of Resistance to Proflavine and Penicillin in Escherichia coli

PubMed Central

McKellar, Robin C.; McKenzie, Colin N.; Kushner, Donn J.

1976-01-01

A number of proflavine (PF)-resistant mutants of Escherichia coli B were also resistant to penicillin and cephalothin. Mutants resistant to 1.0 mM PF were 10 times more penicillin resistant than were the PF-susceptible, wild-type cells. Single-step mutants selected for resistance to either PF or penicillin were also resistant to the other drug. None of the resistant mutants tested possessed β-lactamase activity. These results suggest that resistance to PF and penicillin in E. coli B may be due to permeability changes in the cell envelope. PMID:791110

Varicella-zoster virus complements herpes simplex virus type 1 temperature-sensitive mutants.

PubMed Central

Felser, J M; Straus, S E; Ostrove, J M

1987-01-01

Varicella-zoster virus (VZV) can complement temperature-sensitive mutants of herpes simplex virus. Of seven mutants tested, two, carrying mutations in the immediate-early ICP4 and ICP27 proteins, were complemented. This complementation was not seen in coinfections with adenovirus type 5 or cytomegalovirus. Following transfection into CV-1 cells, a DNA fragment containing the VZV short repeat sequence complemented the ICP4 mutant. These data demonstrate a functional relationship between VZV and herpes simplex virus and have allowed localization of a putative VZV immediate-early gene. PMID:3023701

Distributional properties of relative phase in bimanual coordination.

PubMed

James, Eric; Layne, Charles S; Newell, Karl M

2010-10-01

Studies of bimanual coordination have typically estimated the stability of coordination patterns through the use of the circular standard deviation of relative phase. The interpretation of this statistic depends upon the assumption of a von Mises distribution. The present study tested this assumption by examining the distributional properties of relative phase in three bimanual coordination patterns. There were significant deviations from the von Mises distribution due to differences in the kurtosis of distributions. The kurtosis depended upon the relative phase pattern performed, with leptokurtic distributions occurring in the in-phase and antiphase patterns and platykurtic distributions occurring in the 30° pattern. Thus, the distributional assumptions needed to validly and reliably use the standard deviation are not necessarily present in relative phase data though they are qualitatively consistent with the landscape properties of the intrinsic dynamics.

Occurrence of toxicity among protease, amylase, and color mutants of a nontoxic soy sauce koji mold

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kalayanamitr, A.; Bhumiratana, A.; Flegel, T.W.

A soy sauce koji mold, Aspergillus flavus var. columnaris Raper and Fennel (ATCC 44310), was treated with UV irradiation to obtain mutant strains possessing high protease activities, high amylase activities, and light-colored conidia. Selected mutant strains were tested for toxicity, and some were found acutely toxic to weanling rats, although all were negative for aflatoxin production.

Bildanalyse in Medizin und Biologie

NASA Astrophysics Data System (ADS)

Athelogou, Maria; Schönmeyer, Ralf; Schmidt, Günther; Schäpe, Arno; Baatz, Martin; Binnig, Gerd

Heutzutage sind bildgebende Verfahren aus medizinischen Untersuchungen nicht mehr wegzudenken. Diverse Methoden - basierend auf dem Einsatz von Ultraschallwellen, Röntgenstrahlung, Magnetfeldern oder Lichtstrahlen - werden dabei spezifisch eingesetzt und liefern umfangreiches Datenmaterial über den Körper und sein Inneres. Anhand von Mikroskopieaufnahmen aus Biopsien können darüber hinaus Daten über die morphologische Eigenschaften von Körpergeweben gewonnen werden. Aus der Analyse all dieser unterschiedlichen Arten von Informationen und unter Konsultation weiterer klinischer Untersuchungen aus diversen medizinischen Disziplinen kann unter Berücksichtigung von Anamnesedaten ein "Gesamtbild“ des Gesundheitszustands eines Patienten erstellt werden. Durch die Flut der erzeugten Bilddaten kommt der Bildverarbeitung im Allgemeinen und der Bildanalyse im Besonderen eine immer wichtigere Rolle zu. Gerade im Bereich der Diagnoseunterstützung, der Therapieplanung und der bildgeführten Chirurgie bilden sie Schlüsseltechnologien, die den Forschritt nicht nur auf diesen Gebieten maßgeblich vorantreiben.

[Accumulation of the bvg- Bordetella pertussis a virulent mutants in the process of experimental whooping cough in mice].

PubMed

Medkova, A Iu; Siniashina, L N; Rumiantseva, Iu P; Voronina, O L; Kunda, M S; Karataev, G I

2013-01-01

The duration of the persistence and dynamics of accumulation of insertion bvg- Bordetella pertussis mutants were studied in lungs of laboratory mice after intranasal and intravenous challenge by virulent bacteria of the causative agent of whooping cough. The capability of the virulent B. pertussis bacteria to long-term persistence in the body of mice was tested. Using the real-time PCR approximately hundred genome equivalents of the B. pertussis DNA were detected in lungs of mice in two months after infection regardless of the way of challenge. Using the bacterial test bacteria were identified during only four weeks after challenge. Bvg- B. pertussis avirulent mutants were accumulated for the infection time. The percentage of the avirulent bacteria in the B. pertussis population reached 50% in 7-9 weeks after challenge. The obtained results show that the laboratory mice can be used for study of the B. pertussis insertion mutant formation dynamics in vivo and confirm the hypothesis about insertional bvg- B. pertussis virulent mutants accumulation during development of pertussis infection in human.

Autolytic defective mutant of Streptococcus faecalis.

PubMed Central

Cornett, J B; Redman, B E; Shockman, G D

1978-01-01

Properties of a variant of Streptococcus faecalis ATCC 9790 with defective cellular autolysis are described. The mutant strain was selected as a survivor from a mutagenized cell population simultaneously challenged with two antibiotics which inhibit cell wall biosynthesis, penicillin G and cycloserine. Compared to the parental strain, the mutant strain exhibited: (i) a thermosensitive pattern of cellular autolysis; (ii) an autolytic enzyme activity that had only a slightly increased thermolability when tested in solution in the absence of wall substrate; and (iii) an isolated autolysin that had hydrolytic activity on isolated S. faecalis wall substrate indistinguishable from that of the parental strain, but that was inactive when tested on walls of Micrococcus lysodeikticus as a substrate. These data indicate an alteration in the substrate specificity of the autolytic enzyme of the mutant which appears to result from the synthesis of an altered form of autolytic enzyme. PMID:415045

Cercosporin-deficient mutants by plasmid tagging in the asexual fungus Cercospora nicotianae.

PubMed

Chung, K-R; Ehrenshaft, M; Wetzel, D K; Daub, M E

2003-11-01

We have successfully adapted plasmid insertion and restriction enzyme-mediated integration (REMI) to produce cercosporin toxin-deficient mutants in the asexual phytopathogenic fungus Cercospora nicotianae. The use of pre-linearized plasmid or restriction enzymes in the transformation procedure significantly decreased the transformation frequency, but promoted a complicated and undefined mode of plasmid integration that leads to mutations in the C. nicotianae genome. Vector DNA generally integrated in multiple copies, and no increase in single-copy insertion was observed when enzymes were added to the transformation mixture. Out of 1873 transformants tested, 39 putative cercosporin toxin biosynthesis ( ctb) mutants were recovered that showed altered levels of cercosporin production. Seven ctb mutants were recovered using pre-linearized plasmids without the addition of enzymes, and these were considered to be non-REMI mutants. The correlation between a specific insertion and a mutant phenotype was confirmed using rescued plasmids as gene disruption vectors in the wild-type strain. Six out of fifteen rescued plasmids tested yielded cercosporin-deficient transformants when re-introduced into the wild-type strain, suggesting a link between the insertion site and the cercosporin-deficient phenotype. Sequence analysis of a fragment flanking the insert site recovered from one insertion mutant showed it to be disrupted in sequences with high homology to the acyl transferase domain of polyketide synthases from other fungi. Disruption of this polyketide synthase gene ( CTB1) using a rescued plasmid resulted in mutants that were defective in cercosporin production. Thus, we provide the first molecular evidence that cercosporin is synthesized via a polyketide pathway as previously hypothesized.

Characterization of a Weak Allele of Zebrafish cloche Mutant

PubMed Central

Ma, Ning; Huang, Zhibin; Chen, Xiaohui; He, Fei; Wang, Kun; Liu, Wei; Zhao, Linfeng; Xu, Xiangmin; Liao, Wangjun; Ruan, Hua; Luo, Shenqiu; Zhang, Wenqing

2011-01-01

Hematopoiesis is a complicated and dynamic process about which the molecular mechanisms remain poorly understood. Danio rerio (zebrafish) is an excellent vertebrate system for studying hematopoiesis and developmental mechanisms. In the previous study, we isolated and identified a cloche 172 (clo 172) mutant, a novel allele compared to the original cloche (clo) mutant, through using complementation test and initial mapping. Here, according to whole mount in-situ hybridization, we report that the endothelial cells in clo 172 mutant embryos, although initially developed, failed to form the functional vascular system eventually. In addition, further characterization indicates that the clo 172 mutant exhibited weaker defects instead of completely lost in primitive erythroid cells and definitive hematopoietic cells compared with the clo s5 mutant. In contrast, primitive myeloid cells were totally lost in clo 172 mutant. Furthermore, these reappeared definitive myeloid cells were demonstrated to initiate from the remaining hematopoietic stem cells (HSCs) in clo 172 mutant, confirmed by the dramatic decrease of lyc in clo 172 runx1w84x double mutant. Collectively, the clo 172 mutant is a weak allele compared to the clo s5 mutant, therefore providing a model for studying the early development of hematopoietic and vascular system, as well as an opportunity to further understand the function of the cloche gene. PMID:22132109

Multiaxial constitutive behavior of an interstitial-free steel: Measurements through X-ray and digital image correlation

PubMed Central

Jeong, Y.; Iadicola, M.A.; Gnäupel-Herold, T.; Creuziger, A.

2017-01-01

Constitutive behaviors of an interstitial-free steel sample were measured using an augmented Marciniak experiment. In these tests, multiaxial strain field data of the flat specimens were measured by the digital image correlation technique. In addition, the flow stress was measured using an X-ray diffractometer. The flat specimens in three different geometries were tested in order to achieve 1) balanced biaxial strain, and plane strain tests with zero strain in either 2) rolling direction or 3) transverse direction. The multiaxial stress and strain data were processed to obtain plastic work contours with reference to a uniaxial tension test along the rolling direction. The experimental results show that the mechanical behavior of the subjected specimen deviates significantly from isotropic behavior predicted by the von Mises yield criterion. The initial yield loci measured by a Marciniak tester is in good agreement with what is predicted by Hill's yield criterion. However, as deformation increases beyond the vonMises strain of 0.05, the shape of the work contour significantly deviates from that of Hill's yield locus. A prediction made by a viscoplastic self-consistent model is in better agreement with the experimental observation than the Hill yield locus with the isotropic work-hardening rule. However, none of the studied models matched the initial or evolving anisotropic behaviors of the interstitial-free steel measured by the augmented Marciniak experiment. PMID:28690400

Multiaxial constitutive behavior of an interstitial-free steel: Measurements through X-ray and digital image correlation.

PubMed

Jeong, Y; Iadicola, M A; Gnäupel-Herold, T; Creuziger, A

2016-06-15

Constitutive behaviors of an interstitial-free steel sample were measured using an augmented Marciniak experiment. In these tests, multiaxial strain field data of the flat specimens were measured by the digital image correlation technique. In addition, the flow stress was measured using an X-ray diffractometer. The flat specimens in three different geometries were tested in order to achieve 1) balanced biaxial strain, and plane strain tests with zero strain in either 2) rolling direction or 3) transverse direction. The multiaxial stress and strain data were processed to obtain plastic work contours with reference to a uniaxial tension test along the rolling direction. The experimental results show that the mechanical behavior of the subjected specimen deviates significantly from isotropic behavior predicted by the von Mises yield criterion. The initial yield loci measured by a Marciniak tester is in good agreement with what is predicted by Hill's yield criterion. However, as deformation increases beyond the vonMises strain of 0.05, the shape of the work contour significantly deviates from that of Hill's yield locus. A prediction made by a viscoplastic self-consistent model is in better agreement with the experimental observation than the Hill yield locus with the isotropic work-hardening rule. However, none of the studied models matched the initial or evolving anisotropic behaviors of the interstitial-free steel measured by the augmented Marciniak experiment.

In-phase and out-of-phase axial-torsional fatigue behavior of Haynes 188 at 760 C

NASA Technical Reports Server (NTRS)

Kalluri, Sreeramesh; Bonacuse, Peter J.

1991-01-01

Isothermal, in-phase and out-of-phase axial-torsional fatigue experiments have been conducted at 760 C on uniform gage section, thin-walled tubular specimens of a wrought cobalt-base superalloy, Haynes 188. Test-control and data acquisition were accomplished with a minicomputer. Fatigue lives of the in- and out-of-phase axial-torsional fatigue tests have been estimated with four different multiaxial fatigue life prediction models that were developed primarly for predicting axial-torsional fatigue lives at room temperature. The models investigated were: (1) the von Mises equivalent strain range; (2) the Modified Multiaxiality Factor Approach; (3) the Modified Smith-Watson-Topper Parameter; and (4) the critical shear plane method of Fatemi, Socie, and Kurath. In general, life predictions by the von Mises equivalent strain range model were within a factor of 2 for a majority of the tests and the predictions by the Modified Multiaxiality Factor Approach were within a factor of 2, while predictions of the Modified Smith-Watson-Topper Parameter and of the critical shear plane method of Fatemi, Socie, and Kurath were unconservative and conservative, respectively, by up to factors of 4. In some of the specimens tested under combined axial-torsional loading conditions, fatigue cracks initiated near extensometer indentations. Two design modifications have been proposed to the thin-walled tubular specimen to overcome this problem.

Randall Selitto pressure algometry for assessment of bone-related pain in rats.

PubMed

Falk, S; Ipsen, D H; Appel, C K; Ugarak, A; Durup, D; Dickenson, A H; Heegaard, A M

2015-03-01

Deep pain is neglected compared with cutaneous sources. Pressure algometry has been validated in the clinic for assessment of bone-related pain in humans. In animal models of bone-related pain, we have validated the Randall Selitto behavioural test for assessment of acute and pathological bone pain and compared the outcome with more traditional pain-related behaviour measures. Randall Selitto pressure algometry was performed over the anteromedial part of the tibia in naïve rats, sham-operated rats, and rats inoculated with MRMT-1 carcinoma cells in the left tibia, and the effect of morphine was investigated. Randall Selitto measures of cancer-induced bone pain were supplemented by von Frey testing, weight-bearing and limb use test. Contribution of cutaneous nociception to Randall Selitto measures were examined by local anaesthesia. Randall Selitto pressure algometry over the tibia resulted in reproducible withdrawal thresholds, which were dose-dependently increased by morphine. Cutaneous nociception did not contribute to Randall Selitto measures. In cancer-bearing animals, compared with sham, significant differences in pain-related behaviours were demonstrated by the Randall Selitto test on day 17 and 21 post-surgery. A difference was also demonstrated by von Frey testing, weight-bearing and limb use tests. Our results indicate that pressure applied by the Randall Selitto algometer on a region, where the bone is close to the skin, may offer a way to measure bone-related pain in animal models and could provide a supplement to the traditional behavioural tests and a means to study deep pain. © 2014 European Pain Federation - EFIC®

Victor or Villain? Wernher von Braun and the Space Race

ERIC Educational Resources Information Center

O'Brien, Jason L.; Sears, Christine E.

2011-01-01

Set during the Cold War and space race, this historical role-play focuses on Wernher von Braun's involvement in and culpability for the use of slave laborers to produce V-2 rockets for Nazi Germany. Students will grapple with two central questions. Should von Braun have been allowed to emigrate to the United States given his affiliation with the…

Wernher von Braun

NASA Image and Video Library

1970-02-24

Dr. von Braun was honored with a series of farewell events and ceremonies prior to his reassignment to NASA Headquarters in Washington, D.C. Alabama Governor Brewer greets Dr. von Braun following his speech at the front of the Madison County Courthouse in Huntsville, Alabama on February 24, 1970. Behind are Madison County Commissioner James Record, Huntsville Mayor Joe Davis, and U.S. Senator Sparkman.

Wernher von Braun

NASA Image and Video Library

1969-07-24

Apollo 11 splashdown celebration in Huntsville, Alabama, on July 24, 1969. Huntsville Alabama is the home of the Marshall Space Flight Center which developed the Saturn vehicles under the direction of Dr. von Braun. The photo shows Dr. von Braun speaking to the crowd at the Madison County Courthouse as Mayor Joe Davis, Madison County Commissioner James Record and City Council President Ken Johnson look on.

"'And They Lived Happily Ever After": The Fairy Tale of Radical Constructivism and Von Glasersfeld's Ethical Disengagement

ERIC Educational Resources Information Center

d'Agnese, Vasco

2015-01-01

Is von Glasersfeld's constructivism actually radical? In this article, I respond to this question by analyzing von Glasersfeld's main works. I argue that the essential theoretical move of radical constructivism--namely the assertion that reality is the construction of a human mind that only responds to the subjective perception of "what…

Wernher von Braun

NASA Image and Video Library

1969-07-24

Dr. von Braun is carried aloft on the shoulders of Huntsville city officials during the Apollo 11 celebration in Huntsville, Alabama, on July 24, 1969. Huntsville, Alabama is the home of the Marshall Space Flight Center which developed the Saturn vehicles under the direction of Dr. von Braun. The Apollo 11 lifted off in July and made the first marned lunar landing on the Moon.

The Magic Background of Pearl Harbor. Volume 2 (May 12, 1941 - August 6, 1941)

DTIC Science & Technology

1977-01-01

sistance in an Axis move against India.617 German Ambassador Franz von Papen and Foreign Minister Shukru Saracoglu signed a Turkish-German Pact...sadorB rlinportedTokyonJu7,941thatitw sthpinion of Chancellor Hitler and Foreign Minister von Ribbentrop that the United States would hesi...particularlyinregardtowaragainstEngland,HerrHessmighthavebeenanxioustoleaveGermany.ItwasalsoknownthathepossessedagreatdislikeforForeignMin- ister von

Valence bond and von Neumann entanglement entropy in Heisenberg ladders.

PubMed

Kallin, Ann B; González, Iván; Hastings, Matthew B; Melko, Roger G

2009-09-11

We present a direct comparison of the recently proposed valence bond entanglement entropy and the von Neumann entanglement entropy on spin-1/2 Heisenberg systems using quantum Monte Carlo and density-matrix renormalization group simulations. For one-dimensional chains we show that the valence bond entropy can be either less or greater than the von Neumann entropy; hence, it cannot provide a bound on the latter. On ladder geometries, simulations with up to seven legs are sufficient to indicate that the von Neumann entropy in two dimensions obeys an area law, even though the valence bond entanglement entropy has a multiplicative logarithmic correction.

Molecular quantum control landscapes in von Neumann time-frequency phase space

NASA Astrophysics Data System (ADS)

Ruetzel, Stefan; Stolzenberger, Christoph; Fechner, Susanne; Dimler, Frank; Brixner, Tobias; Tannor, David J.

2010-10-01

Recently we introduced the von Neumann representation as a joint time-frequency description for femtosecond laser pulses and suggested its use as a basis for pulse shaping experiments. Here we use the von Neumann basis to represent multidimensional molecular control landscapes, providing insight into the molecular dynamics. We present three kinds of time-frequency phase space scanning procedures based on the von Neumann formalism: variation of intensity, time-frequency phase space position, and/or the relative phase of single subpulses. The shaped pulses produced are characterized via Fourier-transform spectral interferometry. Quantum control is demonstrated on the laser dye IR140 elucidating a time-frequency pump-dump mechanism.

Molecular quantum control landscapes in von Neumann time-frequency phase space.

PubMed

Ruetzel, Stefan; Stolzenberger, Christoph; Fechner, Susanne; Dimler, Frank; Brixner, Tobias; Tannor, David J

2010-10-28

Recently we introduced the von Neumann representation as a joint time-frequency description for femtosecond laser pulses and suggested its use as a basis for pulse shaping experiments. Here we use the von Neumann basis to represent multidimensional molecular control landscapes, providing insight into the molecular dynamics. We present three kinds of time-frequency phase space scanning procedures based on the von Neumann formalism: variation of intensity, time-frequency phase space position, and/or the relative phase of single subpulses. The shaped pulses produced are characterized via Fourier-transform spectral interferometry. Quantum control is demonstrated on the laser dye IR140 elucidating a time-frequency pump-dump mechanism.

[Scientific theoretical founding of medicine as a natural science by Hermann von Helmholtz (1821-1894)].

PubMed

Neumann, J N

1994-01-01

In this study an attempt will be made to discuss the epistemological problems in the theory and practice of modern technical medicine in the writings of Hermann von Helmholz. An inquiry into the relationship between von Helmholtz' thinking and the critical philosophy of Immanuel Kant is followed by the characteristics of von Helmholtz' philosophy of science which he himself called "empirical theory". The question of medicine as a science finally leads to the main problem of medical epistemology, viz., the relationship between theoretical knowledge and practice in medicine. In this context the anthropological dimension is brought into consideration.

Novel Target for Ameliorating Pain and Other Problems after SCI: Spontaneous Activity in Nociceptors

DTIC Science & Technology

2013-10-01

pretest , post -SCI, and post -TRPV1 intervention). Mechanical hypersensitivity was tested with a single series of cal- ibrated von Frey filaments (Stoelting... test sequence ( pretest , post -SCI, postinjection) [F(2,17) = 11.37; P = 0.007] and drug treat- ment [F(1,11) = 10.70; P = 0.008], with latencies for...revealed a significant effect of the test sequence ( pretest , post -SCI, post -ODN) [F(2,18) = 22.78; P < 0.0001] and ODN treatment [F(1,9) = 11.03; P

Arzt und Hobby-Astronom in stürmischen Zeiten Der Büchernachlass des Doktor Johannes Häringshauser, Viertelsmedicus in Mistelbach (1630-1641) in der Melker Stiftsbibliothek.

NASA Astrophysics Data System (ADS)

Davison, Giles; Glaßner, Gottfried

2009-06-01

Auf der Suche nach astronomischer Literatur stieß Giles Davison in der Melker Stiftsbibliothek auf den Namen "Doctor Johannes Häringshauser“ als Besitzer seltener und interessanter astronomischer Werke u.a. von Johannes Regiomontan, Georg von Peuerbach, Michael Mästlin, Johannes Kepler und Daniel Sennert. Weitere in den Jahren 2007-2009 durchgeführte Nachforschungen ergaben, dass es sich um den von 1630-1641 in Mistelbach, Niederösterreich, als Landschaftsarzt tätigen Vater des Melker Konventualen und Bibliothekars Sigismund Häringshauser (1631-1698) handelt. Er wurde 1603 als Sohn des aus Magdeburg stammenden Apothekers Johannes Häringshauser geboren und starb 1642 in Mistelbach. Johannes Häringshauser Sen. bekleidete von 1613-1640 eine Reihe wichtiger Ämter in der Wiener Stadtregierung und starb 1647. Der Studienaufenthalt von Dr. Johannes Häringshauser Jun. in Padua (1624-1626) dürfte das Interesse für Astronomie geweckt haben, das sich in seiner in die Bestände der Melker Stiftsbibliothek eingegangenen Privatbibliothek widerspiegelt. Der Großteil der 10 dem Fachbereich der Astronomie und Astrologie zuzuweisenden Titel wurde von ihm in den Jahren 1636 und 1637 erworben.

Structure-activity relations of successful pharmacologic chaperones for rescue of naturally occurring and manufactured mutants of the gonadotropin-releasing hormone receptor.

PubMed

Janovick, Jo Ann; Goulet, Mark; Bush, Eugene; Greer, Jonathan; Wettlaufer, David G; Conn, P Michael

2003-05-01

We expressed a test system of wild-type (WT) rat (r) and human (h) gonadotropin-releasing hormone (GnRH) receptors (GnRHRs), including naturally occurring (13) and manufactured (five) "loss-of-function" mutants of the GnRHR. These were used to assess the ability of different GnRH peptidomimetics to rescue defective GnRHR mutants and determine their effect on the level of membrane expression of the WT receptors. Among the manufactured mutants were the shortest rGnRHR C-terminal truncation mutant that resulted in receptor loss-of-function (des(325-327)-rGnRHR), two nonfunctional deletion mutants (des(237-241)-rGnRHR and des(260-265)-rGnRHR), two nonfunctional Cys mutants (C(229)A-rGnRHR and C(278)A-rGnRHR); the naturally occurring mutants included all 13 full-length GnRHR point mutations reported to date that result in full or partial human hypogonadotropic hypogonadism. The 10 peptidomimetics assessed as potential rescue molecules ("pharmacoperones") are from three differing chemical pedigrees (indoles, quinolones, and erythromycin-derived macrolides) and were originally developed as GnRH peptidomimetic antagonists. These structures were selected for this study because of their predicted ability to permeate the cell membrane and interact with a defined affinity with the GnRH receptor. All peptidomimetics studied with an IC(50) value (for hGnRHR)

VIP1 and Its Homologs Are Not Required for Agrobacterium-Mediated Transformation, but Play a Role in Botrytis and Salt Stress Responses

PubMed Central

Lapham, Rachelle; Lee, Lan-Ying; Tsugama, Daisuke; Lee, Sanghun; Mengiste, Tesfaye; Gelvin, Stanton B.

2018-01-01

The bZIP transcription factor VIP1 interacts with the Agrobacterium virulence protein VirE2, but the role of VIP1 in Agrobacterium-mediated transformation remains controversial. Previously tested vip1-1 mutant plants produce a truncated protein containing the crucial bZIP DNA-binding domain. We generated the CRISPR/Cas mutant vip1-2 that lacks this domain. The transformation susceptibility of vip1-2 and wild-type plants is similar. Because of potential functional redundancy among VIP1 homologs, we tested transgenic lines expressing VIP1 fused to a SRDX repression domain. All VIP1-SRDX transgenic lines showed wild-type levels of transformation, indicating that neither VIP1 nor its homologs are required for Agrobacterium-mediated transformation. Because VIP1 is involved in innate immune response signaling, we tested the susceptibility of vip1 mutant and VIP1-SRDX plants to Pseudomonas syringae and Botrytis cinerea. vip1 mutant and VIP1-SRDX plants show increased susceptibility to B. cinerea but not to P. syringae infection, suggesting a role for VIP1 in B. cinerea, but not in P. syringae, defense signaling. B. cinerea susceptibility is dependent on abscisic acid (ABA) which is also important for abiotic stress responses. The germination of vip1 mutant and VIP1-SRDX seeds is sensitive to exogenous ABA, suggesting a role for VIP1 in response to ABA. vip1 mutant and VIP1-SRDX plants show increased tolerance to growth in salt, indicating a role for VIP1 in response to salt stress. PMID:29946325

Studies on the control of development: isolation of Bacillus subtilis mutants blocked early in sporulation and defective in synthesis of highly phosphorylated nucleotides.

PubMed

Rhaese, H J; Hoch, J A; Groscurth, R

1977-03-01

To test our model on the mechanism of initiation of differentiation in Bacillus subtilis, we tested early blocked (stage 0) sporulation mutants for their ability to synthesize highly phosphorylated nucleotides. We also isolated early blocked asporogenous mutants with the aid of the intercalating drug tilorone. Among all mutants tested we found that the spo0F-bearing strain was unable to synthesize adenosine 3'(2')-triphosphate 5'-triphosphate, pppAppp. A revertant of this mutant regained the ability to both sporulate and synthesize pppAppp. Ribosomes of the asporogenous mutant isolated at T2 (2 hr after the end of logarithmic growth) of sporulation, in contrast to the wild type, do not synthesize adenosine 3'(2')-diphosphate 5'-diphosphate, ppApp, or adenosine 3'(2')-diphosphate 5'-triphosphate, pppApp, but synthesize guanosine 3'(2')-diphosphate 5'-diphosphate, ppGpp, and guanosine 3'(2')-diphosphate 5'-triphosphate, pppGpp. This behavior is characteristic of ribosomes from vegetative, not sporulating, cells. Ribosomes from the sporogenous revertant behave like those of the wild type. The results suggest that the spo0F mutation may be a mutation in the structural gene for pppAppp synthetase. The inability to synthesize pppAppp in this strain also prevents the formation of "sporulation-specific ribosomes," i.e., ribosomes that synthetize ppApp and pppApp. The present experiments suggest that the nucleotide pppAppp participates in the initiation of sporulation by triggering a sequencies of events required for the production of heat-resistant spores.

Replication of transformation-defective mutants of the Prague strain of Rous sarcoma virus and isolation of a td mutant from duck-adapted PR-RSV-C.

PubMed

Geryk, J; Mazo, A; Svoboda, J; Hlozánek, I

1980-01-01

The replication of transformation-defective mutants of the Prague strain of Rous sarcoma virus subgroup C was studied using roller cultures. Under such conditions, 10(5)--10(6) infectous units of virus per 0.2 ml were produced, as revealed in both the reverse transcriptase and 16Q complementation tests. A new td daPR-RSV-C mutant was isolated from duck-adapted PR-RSV-C. This mutant replicated in roller cultures with equal efficiency as the original td PR-RSV-C. It was verified that td daPR-RSV-C does not transform chicken fibroblasts, is not oncogenic for 3-week-old chickens and has subgroup C host-range specificity. Both td mutants replicate in duck cells and reach the same titres.

Three-dimensional finite element analysis of the stress distribution pattern in a mandibular first molar tooth restored with five different restorative materials.

PubMed

D'souza, Kathleen Manuela; Aras, Meena Ajay

2017-01-01

Badly broken or structurally compromised posterior teeth are frequently associated with crown/root fracture. Numerous restorative materials have been used to fabricate indirect full-coverage restorations for such teeth. This study aims to evaluate and compare the effect of restorative materials on the stress distribution pattern in a mandibular first molar tooth, under varying loading conditions and to compare the stress distribution pattern in five commonly used indirect restorative materials. Five three-dimensional finite element models representing a mandibular first molar tooth restored with crowns of gold, porcelain fused to metal, composite (Artglass), alumina-based zirconia (In-Ceram Zirconia [ICZ]), and double-layered zirconia-based materials (zirconia core veneered with porcelain, Lava) were constructed, using a Finite Element Analysis Software (ANSYS version 10; ANSYS Inc., Canonsburg, PA, USA). Two loading conditions were applied, simulating maximum bite force of 600 N axially and normal masticatory bite force of 225 N axially and nonaxially. Both all-ceramic crowns allowed the least amount of stress distribution to the surrounding tooth structure. In maximum bite force-simulation test, alumina-based all-ceramic crown displayed the highest von Mises stresses (123.745 MPa). In the masticatory bite force-simulation test, both all-ceramic crowns (122.503-133.13 MPa) displayed the highest von Mises stresses. ICZ crown displayed the highest peak von Mises stress values under maximum and masticatory bite forces. ICZ and Lava crowns also allowed the least amount of stress distribution to the surrounding tooth structure, which is indicative of a favorable response of the underlying tooth structure to the overlying full-coverage indirect restorative material. These results suggest that ICZ and Lava crowns can be recommended for clinical use in cases of badly damaged teeth.

Differential sensitivity of von Willebrand factor (VWF) 'activity' assays to large and small VWF molecular weight forms: a cross-laboratory study comparing ristocetin cofactor, collagen-binding and mAb-based assays.

PubMed

Favaloro, E J; Bonar, R; Chapman, K; Meiring, M; Funk Adcock, D

2012-06-01

von Willebrand disease (VWD), the most common inherited bleeding disorder, is caused by deficiencies and/or defects in von Willebrand factor (VWF). An effective diagnostic and VWD typing strategy requires plasma testing for factor VIII, and VWF antigen plus one or more VWF 'activity' assays. VWF activity is classically assessed by using VWF ristocetin cofactor activity (VWF:RCo), although VWF collagen-binding (VWF:CB) and VWF mAb-based (VWF activity [VWF:Act]) assays are used by some laboratories. To perform a cross-laboratory study to specifically evaluate these three VWF activity assays for comparative sensitivity to loss of high molecular weight (HMW) VWF, representing the form of VWF that is most functionally active and that is absent in some types of VWD, namely 2A and 2B. A set of eight samples, including six selectively representing stepwise reduction in HMW VWF, were tested by 51 different laboratories using a variety of assays. The combined data showed that the VWF:CB and VWF:RCo assays had higher sensitivity to the loss of HMW VWF than did the VWF:Act assay. Moreover, within-method analysis identified better HMW VWF sensitivity of some VWF:CB assays than of others, with all VWF:CB assays still showing better sensitivity than the VWF:Act assay. Differences were also identified between VWF:RCo methodologies on the basis of either platelet aggregometry or as performed on automated analyzers. We believe that these results have significant clinical implications for the diagnosis of VWD and monitoring of its therapy, as well as for the future diagnosis and therapy monitoring of thrombotic thrombocytopenic purpura. © 2012 International Society on Thrombosis and Haemostasis.

Dynamic MEMS devices for multi-axial fatigue and elastic modulus measurement

NASA Astrophysics Data System (ADS)

White, Carolyn D.; Xu, Rui; Sun, Xiaotian; Komvopoulos, Kyriakos

2003-01-01

For reliable MEMS device fabrication and operation, there is a continued demand for precise characterization of materials at the micron scale. This paper presents a novel material characterization device for fatigue lifetime testing. The fatigue specimen is subjected to multi-axial loading, which is typical of most MEMS devices. Polycrystalline silicon (polysilicon) fatigue devices were fabricated using the MUMPS process with a three layer mask process ground plane, anchor, and structural layer of polysilicon. A fatigue device consists of two or three beams, attached to a rotating ring and anchored to the substrate on each end. In order to generate a sufficiently large stress, the fatigue devices were tested in resonance to produce a von Mises equivalent stress as high as 1 GPa, which is in the fracture strength range reported for polysilicon. A further increase of the stress in the beam specimens was obtained by introducing a notch with a focused ion beam. The notch resulted into a stress concentration factor of about 3.8, thereby producing maximum von Mises equivalent stress in the range of 1 through 4 GPa. This study provides insight into multi-axial fatigue testing under typical MEMS conditions and additional information about micron-scale polysilicon mechanical behavior, which is the current basic building material for MEMS devices.

20. HISTORIC VIEW OF THE VEREIN FUER RAUMSCHIFFAHRT, 1930. LEFT ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

20. HISTORIC VIEW OF THE VEREIN FUER RAUMSCHIFFAHRT, 1930. LEFT TO RIGHT: RUDOLF NEBEL, FRANZ RITTER, UNKNOWN, KURT HEINISCH, UNKNOWN, HERMANN OBERTH, UNKNOWN, KLAUS RIEDEL, WERNHER VON BRAUN, UNKNOWN, KLAUS RIEDEL HOLDS EARLY VERSION OR MODEL FOR THE MINIMUM ROCKET, 'MIRAK'. - Marshall Space Flight Center, Redstone Rocket (Missile) Test Stand, Dodd Road, Huntsville, Madison County, AL

Strong Horses-Systems Thinking-Strategic Communication

DTIC Science & Technology

2009-04-30

nature into how strategic leaders think about strategic communication prove salient when attempting to test the system with messages and actions...tools are equal nor found in each government agency. Those tools include but are not limited to: Information and Psychological operations (IO/PSYOP...25 Ludwig von Bertalanffy, General System Theory,1968. 26 Robert Lilienfeld , The Rise in System’s

Synesthesia and Memory: Color Congruency, Von Restorff, and False Memory Effects

ERIC Educational Resources Information Center

Radvansky, Gabriel A.; Gibson, Bradley S.; McNerney, M. Windy

2011-01-01

In the current study, we explored the influence of synesthesia on memory for word lists. We tested 10 grapheme-color synesthetes who reported an experience of color when reading letters or words. We replicated a previous finding that memory is compromised when synesthetic color is incongruent with perceptual color. Beyond this, we found that,…

Childhood Picture of Dr. von Braun

NASA Technical Reports Server (NTRS)

1912-01-01

This is a childhood picture of Dr. von Braun (center) with his brothers. Dr. Wernher von Braun was born in Wirsitz, Germany, March 23, 1912. His childhood dreams of marned space flight were fulfilled when giant Saturn rockets, developed under his direction at NASA's Marshall Space Flight Center, boosted the manned Apollo spacecraft to the Moon. His life was dedicated to expanding man's knowledge through the exploration of space.

Dr. von Braun With German Rocket Experimenters

NASA Technical Reports Server (NTRS)

1930-01-01

Dr. von Braun was among a famous group of rocket experimenters in Germany in the 1930s. This photograph is believed to be made on the occasion of Herman Oberth's Kegelduese liquid rocket engine being certified as to performance during firing. From left to right are R. Nebel, Dr. Ritter, Mr. Baermueller, Kurt Heinish, Herman Oberth, Klaus Riedel, Wernher von Braun, and an unidentified person.

Dr. von Braun Tries Out the Neutral Buoyancy Simulator (NBS)

NASA Technical Reports Server (NTRS)

1967-01-01

Astronaut L. Gordon Cooper checks the neck ring of a space suit worn by Marshall Space Flight Center (MSFC) Director, Dr. von Braun before he submerges into the water of the MSFC Neutral Buoyancy Simulator (NBS). Wearing a pressurized suit and weighted to a neutrally buoyant condition, Dr. von Braun was able to perform tasks underwater which simulated weightless conditions found in space.

(Never) Mind your p's and q's: Von Neumann versus Jordan on the foundations of quantum theory

NASA Astrophysics Data System (ADS)

Duncan, A.; Janssen, M.

2013-03-01

In 1927, in two papers entitled "On a new foundation [Neue Begründung] of quantum mechanics," Pascual Jordan presented his version of what came to be known as the Dirac-Jordan statistical transformation theory. Jordan and Paul Dirac arrived at essentially the same theory independently of one another at around the same time. Later in 1927, partly in response to Jordan and Dirac and avoiding the mathematical difficulties facing their approach, John von Neumann developed the modern Hilbert space formalism of quantum mechanics. We focus on Jordan and von Neumann. Central to the formalisms of both are expressions for conditional probabilities of finding some value for one quantity given the value of another. Beyond that Jordan and von Neumann had very different views about the appropriate formulation of problems in quantum mechanics. For Jordan, unable to let go of the analogy to classical mechanics, the solution of such problems required the identification of sets of canonically conjugate variables, i.e., p's and q's. For von Neumann, not constrained by the analogy to classical mechanics, it required only the identification of a maximal set of commuting operators with simultaneous eigenstates. He had no need for p's and q's. Jordan and von Neumann also stated the characteristic new rules for probabilities in quantum mechanics somewhat differently. Jordan and Dirac were the first to state those rules in full generality. Von Neumann rephrased them and, in a paper published a few months later, sought to derive them from more basic considerations. In this paper we reconstruct the central arguments of these 1927 papers by Jordan and von Neumann and of a paper on Jordan's approach by Hilbert, von Neumann, and Nordheim. We highlight those elements in these papers that bring out the gradual loosening of the ties between the new quantum formalism and classical mechanics. This paper was written as part of a joint project in the history of quantum physics of the Max Planck Institut für Wissenschaftsgeschichte and the Fritz-Haber-Institut in Berlin.

RAS testing of liquid biopsy correlates with the outcome of metastatic colorectal cancer patients treated with first-line FOLFIRI plus cetuximab in the CAPRI-GOIM trial.

PubMed

Normanno, N; Esposito Abate, R; Lambiase, M; Forgione, L; Cardone, C; Iannaccone, A; Sacco, A; Rachiglio, A M; Martinelli, E; Rizzi, D; Pisconti, S; Biglietto, M; Bordonaro, R; Troiani, T; Latiano, T P; Giuliani, F; Leo, S; Rinaldi, A; Maiello, E; Ciardiello, F

2018-01-01

Liquid biopsy is an alternative to tissue for RAS testing in metastatic colorectal carcinoma (mCRC) patients. Little information is available on the predictive role of liquid biopsy RAS testing in patients treated with first-line anti-EGFR monoclonal antibody-based therapy. In the CAPRI-GOIM trial, 340 KRAS exon-2 wild-type mCRC patients received first-line cetuximab plus FOLFIRI. Tumor samples were retrospectively assessed by next generation sequencing (NGS). Baseline plasma samples were analyzed for KRAS and NRAS mutations using beads, emulsion, amplification, and magnetics digital PCR (BEAMing). Discordant cases were solved by droplet digital PCR (ddPCR) or deep-sequencing. A subgroup of 92 patients with available both NGS data on tumor samples and baseline plasma samples were included in this study. Both NGS analysis of tumor tissue and plasma testing with BEAMing identified RAS mutations in 33/92 patients (35.9%). However, 10 cases were RAS tissue mutant and plasma wild-type, and additional 10 cases were tissue wild-type and plasma mutant, resulting in a concordance rate of 78.3%. Analysis of plasma samples with ddPCR detected RAS mutations in 2/10 tissue mutant, plasma wild-type patients. In contrast, in all tissue wild-type and plasma mutant cases, ddPCR or deep-sequencing analysis of tumor tissue confirmed the presence of RAS mutations at allelic frequencies ranging between 0.15% and 1.15%. The median progression-free survival of RAS mutant and wild-type patients according to tissue (7.9 versus 12.6 months; P = 0.004) and liquid biopsy testing (7.8 versus 13.8 moths; P < 0.001) were comparable. Similar findings were observed for the median overall survival of RAS mutant and wild-type patients based on tissue (22.1 versus 35.8 months; P = 0.016) and plasma (19.9 versus 35.8 months; P = 0.013) analysis. This study indicates that RAS testing of liquid biopsy results in a similar outcome when compared with tissue testing in mCRC patients receiving first-line anti-EGFR monoclonal antibodies. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Intracistronic complementation in the simian virus 40 A gene.

PubMed Central

Tornow, J; Cole, C N

1983-01-01

A set of eight simian virus 40 mutants was constructed with lesions in the A gene, which encodes the large tumor (T) antigen. These mutants have small deletions (3-20 base pairs) at either 0.497, 0.288, or 0.243 map units. Mutants having both in-phase and frameshift mutations at each site were isolated. Neither plaque formation nor replication of the mutant DNAs could be detected after transfection of monkey kidney cells. Another nonviable mutant, dlA2459, had a 14-base-pair deletion at 0.193 map unit and was positive for viral DNA replication. Each of the eight mutants were tested for ability to form plaques after cotransfection with dlA2459 DNA. The four mutants that had in-phase deletions were able to complement dlA2459. The other four, which had frameshift deletions, did not. No plaques were formed after cotransfection of cells with any other pair of group A mutants. This suggests that the defect in dlA2459 defines a distinct functional domain of simian virus 40 T antigen. Images PMID:6312452

C. elegans and mutants with chronic nicotine exposure as a novel model of cancer phenotype.

PubMed

Kanteti, Rajani; Dhanasingh, Immanuel; El-Hashani, Essam; Riehm, Jacob J; Stricker, Thomas; Nagy, Stanislav; Zaborin, Alexander; Zaborina, Olga; Biron, David; Alverdy, John C; Im, Hae Kyung; Siddiqui, Shahid; Padilla, Pamela A; Salgia, Ravi

2016-01-01

We previously investigated MET and its oncogenic mutants relevant to lung cancer in C. elegans. The inactive orthlogues of the receptor tyrosine kinase Eph and MET, namely vab-1 and RB2088 respectively, the temperature sensitive constitutively active form of KRAS, SD551 (let-60; GA89) and the inactive c-CBL equivalent mutants in sli-1 (PS2728, PS1258, and MT13032) when subjected to chronic exposure of nicotine resulted in a significant loss in egg-laying capacity and fertility. While the vab-1 mutant revealed increased circular motion in response to nicotine, the other mutant strains failed to show any effect. Overall locomotion speed increased with increasing nicotine concentration in all tested mutant strains except in the vab-1 mutants. Moreover, chronic nicotine exposure, in general, upregulated kinases and phosphatases. Taken together, these studies provide evidence in support of C. elegans as initial in vivo model to study nicotine and its effects on oncogenic mutations identified in humans.

SELF-STERILE AUXOTROPHS AND THEIR RELATION TO HETEROTHALLISM IN SORDARIA FIMICOLA.

PubMed

EL-ANI, A S

1964-09-04

Eighty morphological mutants in the homothallic fungus Sordaria fimicola were tested on liquid minimal medium for nutritional requirements. Five had nutritional requirements, one for adenine, three for arginine, and one for lysine. All five were from among the eighty single gene mutants that were also partially or completely self-sterile. Nutritional requirements and centromere-locus intervals provide better criteria than morphological characters for selecting self-sterile mutants at complex loci governing heterothallism.

Theory and Modeling of Liquid Explosive Detonation

NASA Astrophysics Data System (ADS)

Tarver, Craig M.; Urtiew, Paul A.

2010-10-01

The current understanding of the detonation reaction zones of liquid explosives is discussed in this article. The physical and chemical processes that precede and follow exothermic chemical reaction within the detonation reaction zone are discussed within the framework of the nonequilibrium Zeldovich-von Neumann-Doring (NEZND) theory of self-sustaining detonation. Nonequilibrium chemical and physical processes cause finite time duration induction zones before exothermic chemical energy release occurs. This separation between the leading shock wave front and the chemical energy release needed to sustain it results in shock wave amplification and the subsequent formation of complex three-dimensional cellular structures in all liquid detonation waves. To develop a practical Zeldovich-von Neumann-Doring (ZND) reactive flow model for liquid detonation, experimental data on reaction zone structure, confined failure diameter, unconfined failure diameter, and failure wave velocity in the Dremin-Trofimov test for detonating nitromethane are calculated using the ignition and growth reactive flow model.

Animal Models of Hemophilia and Related Bleeding Disorders

PubMed Central

Lozier, Jay N.; Nichols, Timothy C.

2013-01-01

Animal models of hemophilia and related diseases are important for development of novel treatments and to understand the pathophysiology of bleeding disorders in humans. Testing in animals with the equivalent human disorder provides informed estimates of doses and measures of efficacy, which aids in design of human trials. Many models of hemophilia A, hemophilia B, and von Willebrand disease have been developed from animals with spontaneous mutations (hemophilia A dogs, rats, sheep; hemophilia B dogs; and von Willebrand disease pigs and dogs), or by targeted gene disruption in mice to create hemophilia A, B, or VWD models. Animal models have been used to generate new insights into the pathophysiology of each bleeding disorder and also to perform pre-clinical assessments of standard protein replacement therapies as well as novel gene transfer technology. Both the differences between species and differences in underlying causative mutations must be considered in choosing the best animal for a specific scientific study PMID:23956467

Boden

NASA Astrophysics Data System (ADS)

Pfeiffer, Eva-Maria; Eschenbach, Annette; Munch, Jean Charles

Auch wenn die Risiken bisher kaum quantifizierbar sind, ist davon auszugehen, dass aufgrund der Einbindung des Bodens in die Energie-, Wasser- und Stoffkreisläufe die zu erwartenden Temperatur- und Niederschlagsänderungen die Funktionen dieser zentralen Lebensgrundlage auch in Deutschland gefährden. Nach einer Darstellung der Vielfältigkeit von Böden geht es in diesem Kapitel um mögliche Änderungen der Standortfunktion von Böden und der Leistungen im Ökosystem sowie um den Bodenwasserhaushalt. An herausgehobener Stelle diskutieren die Autoren die Klimafunktion von Böden und stellen mögliche Strategien zu ihrem Schutz vor. Eine große Rolle spielt die Verschränkung mit den anderen Themenbereichen von Teil III, etwa Landwirtschaft, Forstwirtschaft und Wasser.

Effects of mutations within the SV40 large T antigen ATPase/p53 binding domain on viral replication and transformation.

PubMed

Peden, K W; Srinivasan, A; Vartikar, J V; Pipas, J M

1998-01-01

The simian virus 40 (SV40) large T antigen is a 708 amino-acid protein possessing multiple biochemical activities that play distinct roles in productive infection or virus-induced cell transformation. The carboxy-terminal portion of T antigen includes a domain that carries the nucleotide binding and ATPase activities of the protein, as well as sequences required for T antigen to associate with the cellular tumor suppressor p53. Consequently this domain functions both in viral DNA replication and cellular transformation. We have generated a collection of SV40 mutants with amino-acid deletions, insertions or substitutions in specific domains of the protein. Here we report the properties of nine mutants with single or multiple substitutions between amino acids 402 and 430, a region thought to be important for both the p53 binding and ATPase functions. The mutants were examined for the ability to produce infectious progeny virions, replicate viral DNA in vivo, perform in trans complementation tests, and transform established cell lines. Two of the mutants exhibited a wild-type phenotype in all these tests. The remaining seven mutants were defective for plaque formation and viral DNA replication, but in each case these defects could be complemented by a wild-type T antigen supplied in trans. One of these replication-defective mutants efficiently transformed the REF52 and C3H10T1/2 cell lines as assessed by the dense-focus assay. The remaining six mutants were defective for transforming REF52 cells and transformed the C3H10T1/2 line with a reduced efficiency. The ability of mutant T antigen to transform REF52 cells correlated with their ability to induce increased levels of p53.

Signature-tagged mutagenesis screening revealed a novel smooth-to-rough transition determinant of Salmonella enterica serovar Enteritidis.

PubMed

Jiao, Yang; Guo, Rongxian; Tang, Peipei; Kang, Xilong; Yin, Junlei; Wu, Kaiyue; Geng, Shizhong; Li, Qiuchun; Sun, Jun; Xu, Xiulong; Zhou, Xiaohui; Gan, Junji; Jiao, Xinan; Liu, Xiufan; Pan, Zhiming

2017-03-03

Salmonella enterica serovar Enteritidis (S. Enteritidis) has emerged as one of the most important food-borne pathogens for humans. Lipopolysaccharide (LPS), as a component of the outer membrane, is responsible for the virulence and smooth-to-rough transition in S. Enteritidis. In this study, we screened S. Enteritidis signature-tagged transposon mutant library using monoclonal antibody against somatic O 9 antigen (O 9 MAb) and O 9 factor rabbit antiserum to identify novel genes that are involved in smooth-to-rough transition. A total of 480 mutants were screened and one mutant with transposon insertion in rfbG gene had smooth-to-rough transition phenotype. In order to verify the role of rfbG gene, an rfbG insertion or deletion mutant was constructed using λ-Red recombination system. Phenotypic and biological analysis revealed that rfbG insertion or deletion mutants were similar to the wild-type strain in growth rate and biochemical properties, but the swimming motility was reduced. SE Slide Agglutination test and ELISA test showed that rfbG mutants do not stimulate animals to produce agglutinating antibody. In addition, the half-lethal dose (LD 50 ) of the rfbG deletion mutant strain was 10 6.6 -fold higher than that of the parent strain in a mouse model when injected intraperitoneally. These data indicate that the rfbG gene is involved in smooth-to-rough transition, swimming motility and virulence of S. Enteritidis. Furthermore, somatic O-antigen antibody-based approach to screen signature-tagged transposon mutants is feasible to clarify LPS biosynthesis and to find suitable markers in DIVA-vaccine research.

Characterization of three Agrobacterium tumefaciens avirulent mutants with chromosomal mutations that affect induction of vir genes.

PubMed

Metts, J; West, J; Doares, S H; Matthysse, A G

1991-02-01

Three Agrobacterium tumefaciens mutants with chromosomal mutations that affect bacterial virulence were isolated by transposon mutagenesis. Two of the mutants were avirulent on all hosts tested. The third mutant, Ivr-211, was a host range mutant which was avirulent on Bryophyllum diagremontiana, Nicotiana tabacum, N. debneyi, N. glauca, and Daucus carota but was virulent on Zinnia elegans and Lycopersicon esculentum (tomato). That the mutant phenotype was due to the transposon insertion was determined by cloning the DNA containing the transposon insertion and using the cloned DNA to replace the wild-type DNA in the parent bacterial strain by marker exchange. The transposon insertions in the three mutants mapped at three widely separated locations on the bacterial chromosome. The effects of the mutations on various steps in tumor formation were examined. All three mutants showed no alteration in binding to carrot cells. However, none of the mutants showed any induction of vir genes by acetosyringone under conditions in which the parent strain showed vir gene induction. When the mutant bacteria were examined for changes in surface components, it was found that all three of the mutants showed a similar alteration in lipopolysaccharide (LPS). LPS from the mutants was larger in size and more heavily saccharide substituted than LPS from the parent strain. Two of the mutants showed no detectable alteration in outer membrane and periplasmic space proteins. The third mutant, Ivr-225, was missing a 79-kDa surface peptide. The reason(s) for the failure of vir gene induction in these mutants and its relationship, if any, to the observed alteration in LPS are unknown.

Interaktive Visualisierung von Abständen und Ausdehnungen anatomischer Strukturen für die Interventionsplanung

NASA Astrophysics Data System (ADS)

Rössling, Ivo; Cyrus, Christian; Dornheim, Lars; Hahn, Peter; Preim, Bernhard; Boehm, Andreas

Im Rahmen der Interventionsplanung muss der Chirurg therapierelevante Entscheidungen auf Basis räumlicher Relationen anatomischer Strukturen treffen. Interaktive 3D-Visualisierungen unterstützen diesen Prozess qualitativ. Quantitative Fragestellungen (Tumorausdehnung, Infiltrationstiefe, etc.) erfordern die Integration einer Bemaßung, deren Nutzen wesentlich von einer geeigneten Darstellung abhängt. In dieser Arbeit haben wir allgemeine Kriterien für die Eignung von Visualisierungen von Bemaßungen in interaktiven 3D-Szenen erarbeitet. Daran orientierend haben wir verschiedene Varianten der Darstellung von Abständen und Ausdehnungen anatomischer Strukturen betrachtet und ihr Erscheinungsbild hierzu zweckmäßig parametrisiert. Die Ausprägungen dieser Darstellungsparameter wurden in einer Studie auf ihre visuellen Wirkung hin an Chirurgen evaluiert. Es zeigte sich, dass die befragten Mediziner höchsten Wert auf Kohärenz und klare Zuordnung der Bemaßung setzten und überraschenderweise dafür sogar Abstriche in der direkten Lesbarkeit in Kauf nahmen.

Einstellung und Wissen von Lehramtsstudierenden zur Evolution - ein Vergleich zwischen Deutschland und der Türkei

NASA Astrophysics Data System (ADS)

Graf, Dittmar; Soran, Haluk

Es wird eine Untersuchung vorgestellt, in der Wissen und Überzeugungen von Lehramtsstudierenden aller Fächer zum Thema Evolution an zwei Universitäten in Deutschland und der Türkei erhoben worden sind. Die Befragung wurde in Dortmund und in Ankara durchgeführt. Es stellte sich heraus, dass ausgeprägte Defizite im Verständnis der Evolutionsmechanismen herrschen. Viele Studierende, insbesondere aus der Türkei, sind nicht von der Faktizität der Evolution überzeugt. Dies gilt sowohl für Studierende mit Fach Biologie als auch für Studierende mit anderen Fächern. Näher untersucht worden sind die Faktoren, die die Überzeugungen zur Evolution beeinflussen können, was ja in Anbetracht der hohen Ablehnungsrate der Evolution von besonderem Interesse ist. Das Vertrauen in die Wissenschaft spielt hierbei eine besondere Rolle: Wer der Wissenschaft vertraut, ist auch eher von der Evolution überzeugt, als diejenigen, die skeptisch gegenüber der Wissenschaft sind.

Von Kármán between Aachen and Pasadena

NASA Astrophysics Data System (ADS)

Krause, Egon; Kalkmann, Ulrich

2013-05-01

In the Introduction the reader is referred back to the academic ceremonials held after Theodore von Kármán's death in Aachen in May 1963. His work as the first director of the Aerodynamisches Institut (Institute of Aerodynamics) of the RWTH Aachen University of Technology from 1913 on and his initiative to re-establish international cooperation after World War I, resulting in the International Union of Theoretical and Applied Mechanics (IUTAM), are commented on. The following chapter describes von Kármán's relation to his former teacher Ludwig Prandtl. Some of von Kármán's scientific contributions during his time in Aachen are briefly reviewed. Thereafter, his first contacts to the California Institute of Technology are covered. Finally, the scientific and political circumstances, which led to von Kármán's decision to leave Germany in the early thirties, are elucidated in some detail. The English translation of the titles of the Aachen papers is given in Appendix I.

Echinocandin Susceptibility Testing of Candida Species: Comparison of EUCAST EDef 7.1, CLSI M27-A3, Etest, Disk Diffusion, and Agar Dilution Methods with RPMI and IsoSensitest Media▿

PubMed Central

Arendrup, Maiken Cavling; Garcia-Effron, Guillermo; Lass-Flörl, Cornelia; Lopez, Alicia Gomez; Rodriguez-Tudela, Juan-Luis; Cuenca-Estrella, Manuel; Perlin, David S.

2010-01-01

This study compared nine susceptibility testing methods and 12 endpoints for anidulafungin, caspofungin, and micafungin with the same collection of blinded FKS hot spot mutant (n = 29) and wild-type isolates (n = 94). The susceptibility tests included EUCAST Edef 7.1, agar dilution, Etest, and disk diffusion with RPMI-1640 plus 2% glucose (2G) and IsoSensitest-2G media and CLSI M27A-3. Microdilution plates were read after 24 and 48 h. The following test parameters were evaluated: fks hot spot mutants overlapping the wild-type distribution, distance between the two populations, number of very major errors (VMEs; fks mutants misclassified as susceptible), and major errors (MEs; wild-type isolates classified as resistant) using a wild-type-upper-limit value (WT-UL) (two twofold-dilutions higher than the MIC50) as the susceptibility breakpoint. The methods with the lowest number of errors (given as VMEs/MEs) across the three echinocandins were CLSI (12%/1%), agar dilution with RPMI-2G medium (14%/0%), and Etest with RPMI-2G medium (8%/3%). The fewest errors overall were observed for anidulafungin (4%/1% for EUCAST, 4%/3% for CLSI, and 3%/9% for Etest with RPMI-2G). For micafungin, VME rates of 10 to 71% were observed. For caspofungin, agar dilution with either medium was superior (VMEs/MEs of 0%/1%), while CLSI, EUCAST with IsoSensitest-2G medium, and Etest were less optimal (VMEs of 7%, 10%, and 10%, respectively). Applying the CLSI breakpoint (S ≤ 2 μg/ml) for CLSI results, 89.2% fks hot spot mutants were classified as anidulafungin susceptible, 60.7% as caspofungin susceptible, and 92.9% as micafungin susceptible. In conclusion, no test was perfect, but anidulafungin susceptibility testing using the WT-UL to define susceptibility reliably identified fks hot spot mutants. PMID:19884370

Dr. von Braun with Original Mercury Astronauts

NASA Technical Reports Server (NTRS)

1959-01-01

Dr. Wernher von Braun, Director of the Army Ballistic Missile Agency's (ABMA) Development Operations Division, poses with the original Mercury astronauts in ABMA's Fabrication Laboratory during a 1959 visit. Inspecting Mercury-Redstone hardware are from left to right, Alan Shepard, Donald Deke Slayton, Virgil Gus Grissom, von Braun, Gordon Cooper, Wally Schirra, John Glenn, and Scott Carpenter. Project Mercury officially began October 7, 1958 as the United States' first manned space program.

In memory of Eugene (Jenő) von Gothard: a pioneering nineteenth century Hungarian astrophysicist

NASA Astrophysics Data System (ADS)

Vincze, Ildikő J.; Jankovics, István

2012-07-01

Eugene von Gothard was a Hungarian engineer/scientist, instrument-maker and astrophysicist who founded the Herény Astrophysical Observatory in 1881 and carried out pioneering work in astronomical photography and spectroscopy. In this paper we provide biographical material about von Gothard and describe his observatory, before discussing his astronomical observations and the contribution that hemade to the early development of astrophysics.

n/a

NASA Image and Video Library

1965-04-13

Dr. von Braun began his association with Walt Disney in the 1950s when the rocket scientist appeared in three Disney television productions related to the exploration of space. Years later, Dr. von Braun invited Disney and his associates to tour the Marshall Space Flight Center (MSFC) in Huntsville, Alabama. This photograph is dated April 13, 1965. From left are R.J. Schwinghamer from the MSFC, Disney, B.J. Bennight, and Dr. von Braun.

Ebenen des Verstehens: Überlegungen zu einem Verfahren zum Wurzelziehen

NASA Astrophysics Data System (ADS)

Winter, Martin

Wir bemühen uns, insbesondere bei Kindern, den Lernprozess auch im Mathematikunterricht durch den Einsatz von Materialien zu unterstützen. Die Arbeitsschritte dienen dabei oft der Vorbereitung oder Herleitung von Verfahren - in der Hoffnung, dass durch die Veranschaulichung Zusammenhänge besser verstanden werden. Worin dann das Verstehen besteht, wenn im Ergebnis ein Verfahren von den Kindern erfolgreich abgearbeitet wird, ist nicht unmittelbar zu sehen.

Laboratory diagnosis of von Willebrand's disease.

PubMed

Rick, M E

1994-12-01

The diagnosis of von Willebrand's disease is becoming complex as more is understood about the disease. Clinical information and laboratory data are necessary for the diagnosis because of the overlap of normal and abnormal laboratory values. A complete evaluation including von Willebrand factor multimers, ristocetin-induced platelet aggregation, factor VIII activity level, and a template bleeding time is necessary to correctly classify the patient so that optimal treatment may be given.

Distance Estimation to Flashes in a Simulated Night Vision Environment

DTIC Science & Technology

2007-12-01

indirect perception, which has influenced theorists since, is Hermann von Helmholtz’s theory of unconscious conclusions or unconscious inference [6...Goldstein et al. (Eds.), Blackwell handbook of perception (pp. 53-91). Malden, MA: Blackwell Publishers. [6] Helmholtz, H. von (1867/1925). Treatise on...physiological optics (from 3rd German edition, Vol. III). New York: Dover Publications. [7] Helmholtz, H. von (1878/1968). The facts of perception. In

Joint Capabilities for Post-Conflict Operations

DTIC Science & Technology

2004-05-01

Political Geography (NY: John Wiley & Sons, 1989), 37. 2 Karin von Hippel , “Democracy by Force: A Renewed Commitment to Nation Building,” The...fear. Democratic states are vital to international security. In an article adapted from her book, Democracy by Force, Karin von Hippel , a civil...Parameters 33 (Autumn 2003) 101. 5 Karin von Hippel , “Democracy by Force: A Renewed Commitment to Nation Building,” The Washington Quarterly 23 (Winter

Toward an Extension of Decision Analysis to Competitive Situations.

DTIC Science & Technology

1985-12-01

order to deal with competition may ease the use of non- von Neumann-Morgenstern utility. This leads to our secondary goal of questioning expected...While von WInterfeldt [1980] attempted a 5 (more detailed analysis using three separate decision trees, one for each side In the dispute, he felt that...rationality generally used In game theory derives from the same roots as the calculated rationality of Decision Analysis, von Neumann and

Alien: How Operational Art Devoured Strategy

DTIC Science & Technology

2009-09-01

framework to direct it was required. By 1895 at the latest, one had emerged, here described by Baron Colmar Von der Goltz : In the course of...meet the 1895 von der Goltz definition of an “operation” and are entirely consonant with Russian and German thinking.102 As such, they demonstrated...part oF it Strategical and tactical matters often flow into each other. Von der Goltz , 1895 The kind of

An MRI Von Economo - Koskinas atlas.

PubMed

Scholtens, Lianne H; de Reus, Marcel A; de Lange, Siemon C; Schmidt, Ruben; van den Heuvel, Martijn P

2018-04-15

The cerebral cortex displays substantial variation in cellular architecture, a regional patterning that has been of great interest to anatomists for centuries. In 1925, Constantin von Economo and George Koskinas published a detailed atlas of the human cerebral cortex, describing a cytoarchitectonic division of the cortical mantle into over 40 distinct areas. Von Economo and Koskinas accompanied their seminal work with large photomicrographic plates of their histological slides, together with tables containing for each described region detailed morphological layer-specific information on neuronal count, neuron size and thickness of the cortical mantle. Here, we aimed to make this legacy data accessible and relatable to in vivo neuroimaging data by constructing a digital Von Economo - Koskinas atlas compatible with the widely used FreeSurfer software suite. In this technical note we describe the procedures used for manual segmentation of the Von Economo - Koskinas atlas onto individual T1 scans and the subsequent construction of the digital atlas. We provide the files needed to run the atlas on new FreeSurfer data, together with some simple code of how to apply the atlas to T1 scans within the FreeSurfer software suite. The digital Von Economo - Koskinas atlas is easily applicable to modern day anatomical MRI data and is made publicly available online. Copyright © 2017 Elsevier Inc. All rights reserved.

Verantwortlicher Umgang mit Antibiotika: Notwendigkeit der Antibiotikareduktion in der Aknetherapie.

PubMed

Gollnick, Harald P M; Buer, Jan; Beissert, Stefan; Sunderkätter, Cord

2016-12-01

Der übermäßige oder unkritische weltweite Einsatz von Antibiotika in der Medizin hat die Ausbreitung von Antibiotikaresistenzen beschleunigt. In einigen Bereichen sind viele Antibiotika bei bakteriellen Infektionen, die zuvor noch gut auf antibakterielle Wirkstoffe reagierten, mittlerweile wirkungslos geworden. Dermatologen/Venerologen setzten orale und topische Antibiotika bei der Behandlung von Acne vulgaris routinemäßig ein, obwohl Akne weder eine infektiöse Erkrankung ist noch alleine durch das Propionibacterium getriggert wird. Vielmehr ist sie eine komplexe, chronische entzündliche Hauterkrankung, die durch verschiedene pathogenetische Faktoren wie follikuläre Hyperkeratose, erhöhter Sebumproduktion, bakterielle Proliferation und Entzündung zustande kommt. Folglich sollte eine erfolgreiche Therapie auf die Bekämpfung verschiedener pathogenetischer Faktoren und nicht nur auf die von Propionibacterium acnes abzielen. Daher wurden topische Retinoide und Benzoylperoxid als Mittel der ersten Wahl definiert. Monotherapien mit lokalen Antibiotika sollten insgesamt vermieden werden. Systemische Antibiotika der Tetrazyklin-Gruppe haben bei bestimmen Krankheitsstadien ihren Sinn, ihre Wirkung könnte aber eher auf der antientzündlichen als auf der antibiotischen Reaktion beruhen. Gesundheitsbehörden ermahnen alle Gesundheitsdienstleister, den Einsatz von Antibiotika einzuschränken. Das Nutzen-Risiko-Verhältnis muss bei der Entscheidung für oder gegen eine antibiotische Therapie bei einem einzelnen Patienten immer auch in Bezug auf das öffentliche Interesse am Erhalt der Wirksamkeit von Antibiotika abgewogen werden. Im Folgenden werden das aktuelle Krankheitskonzept zu Acne vulgaris und die sich daraus ableitenden Konsequenzen für den Einsatz von Antibiotika vorgestellt. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Neuroretinal hypoxic signaling in a new preclinical murine model for proliferative diabetic retinopathy

PubMed Central

Wert, Katherine J; Mahajan, Vinit B; Zhang, Lijuan; Yan, Yuanqing; Li, Yao; Tosi, Joaquin; Wei Hsu, Chun; Nagasaki, Takayuki; Janisch, Kerstin M; Grant, Maria B; Mahajan, MaryAnn; Bassuk, Alexander G; Tsang, Stephen H

2016-01-01

Diabetic retinopathy (DR) affects approximately one-third of diabetic patients and, if left untreated, progresses to proliferative DR (PDR) with associated vitreous hemorrhage, retinal detachment, iris neovascularization, glaucoma and irreversible blindness. In vitreous samples of human patients with PDR, we found elevated levels of hypoxia inducible factor 1 alpha (HIF1α). HIFs are transcription factors that promote hypoxia adaptation and have important functional roles in a wide range of ischemic and inflammatory diseases. To recreate the human PDR phenotype for a preclinical animal model, we generated a mouse with neuroretinal-specific loss of the von Hippel Lindau tumor suppressor protein, a protein that targets HIF1α for ubiquitination. We found that the neuroretinal cells in these mice overexpressed HIF1α and developed severe, irreversible ischemic retinopathy that has features of human PDR. Rapid progression of retinopathy in these mutant mice should facilitate the evaluation of therapeutic agents for ischemic and inflammatory blinding disorders. In addition, this model system can be used to manipulate the modulation of the hypoxia signaling pathways, for the treatment of non-ocular ischemic and inflammatory disorders. PMID:27195131

LOSS OF JAK2 REGULATION VIA VHL-SOCS1 E3 UBIQUITIN HETEROCOMPLEX UNDERLIES CHUVASH POLYCYTHEMIA

PubMed Central

Russell, Ryan C.; Sufan, Roxana I.; Zhou, Bing; Heir, Pardeep; Bunda, Severa; Sybingco, Stephanie S.; Greer, Samantha N.; Roche, Olga; Heathcote, Samuel A.; Chow, Vinca W.K.; Boba, Lukasz M.; Richmond, Terri D.; Hickey, Michele M.; Barber, Dwayne L.; Cheresh, David A.; Simon, M. Celeste; Irwin, Meredith S.; Kim, William Y.; Ohh, Michael

2011-01-01

SUMMARY Chuvash polycythemia (CP) is a rare congenital form of polycythemia caused by homozygous R200W and H191D mutations in the von Hippel-Lindau (VHL) gene whose gene product is the principal negative regulator of hypoxia-inducible factor. However, the molecular mechanisms underlying some of the hallmark features of CP such as hypersensitivity to erythropoietin are unclear. Here, we show that VHL directly binds suppressor of cytokine signalling 1 (SOCS1) to form a heterodimeric E3 ligase that targets phosphorylated (p)JAK2 for ubiquitin-mediated destruction. In contrast, CP-associated VHL mutants have altered affinity for SOCS1 and fail to engage and degrade pJAK2. Systemic administration of a highly selective JAK2 inhibitor, TG101209, reverses the disease phenotype in vhlR200W/R200W knock-in mice, a model that faithfully recapitulates human CP. These results reveal VHL as a SOCS1-cooperative negative regulator of JAK2 and provide compelling biochemical and preclinical evidence for JAK2- targeted therapy in CP patients. PMID:21685897

Baron von Zach's business relations with the Munich entrepreneur Joseph von Utzschneider (German Title: Geschäftsbeziehungen des Barons von Zach zu dem Münchner Unternehmer Joseph von Utzschneider)

NASA Astrophysics Data System (ADS)

Schneider, Ivo

The relationship between the astronomer von Zach on the one side and the entrepreneur Joseph von Utzschneider and his partner Georg von Reichenbach on the other dates presumably from the year 1807 when Zach spent two months in Munich. Already in the same year Zach had ordered an instrument for himself and began to solicit business for the institute of Reichenbach, Utzschneider, and Liebherr, which was founded in 1804. One of the clients canvassed by Zach was the director of the observatory in Naples Zuccari. Zuccari had ordered the whole equipment for the new observatory from this institute in 1813. The instruments for Naples, which were completed in 1814, were sent accompanied by Reichenbach by land and sea to their destination where Reichenbach supervised their setup. At that time Reichenbach had separated from Utzschneider who kept the optical institute in Benediktbeuern with his new partner Joseph von Fraunhofer whereas Reichenbach became owner of the mathematical-mechanical institute in Munich. For personal and economical reasons Utzschneider began soon after to produce not only optical glass but also optical devices similar to those offered by Reichenbach. As soon as two institutes in Munich competed against each other on the market for sophisticated geodetical and astronomical instruments Zach sided with Utzschneider. Zach's main professional argument for this decision was that both competitors got the optical glass for their instruments from Utzschneider's optical institute in Benediktbeuern. This meant that Utzschneider had first choice and so the optical part of his instruments could be considered as better than that of Reichenbach`s instruments. Zach's role as an agent in Italy and France for the sale of products coming from Utzschneider's manufactories is highlighted by three of Zach's letters to Utzschneider from 1817 and 1818, two of which are reproduced here for the first time.

Lack of promoter IV-driven BDNF transcription results in depression-like behavior.

PubMed

Sakata, K; Jin, L; Jha, S

2010-10-01

Transcription of Bdnf is controlled by multiple promoters, in which promoter IV contributes significantly to activity-dependent Bdnf transcription. We have generated promoter IV mutant mice [brain-derived neurotrophic factor (BDNF)-KIV] in which promoter IV-driven expression of BDNF is selectively disrupted by inserting a green fluorescent protein (GFP)-STOP cassette within the Bdnf exon IV locus. BDNF-KIV animals exhibited depression-like behavior as shown by the tail suspension test (TST), sucrose preference test (SPT) and learned helplessness test (LHT). In addition, BDNF-KIV mice showed reduced activity in the open field test (OFT) and reduced food intake in the novelty-suppressed feeding test (NSFT). The mutant mice did not display anxiety-like behavior in the light and dark box test and elevated plus maze tests. Interestingly, the mutant mice showed defective response inhibition in the passive avoidance test (PAT) even though their learning ability was intact when measured with the active avoidance test (AAT). These results suggest that promoter IV-dependent BDNF expression plays a critical role in the control of mood-related behaviors. This is the first study that directly addressed the effects of endogenous promoter-driven expression of BDNF in depression-like behavior. © 2010 The Authors. Genes, Brain and Behavior © 2010 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

Motor coordination in mice with hotfoot, Lurcher, and double mutations of the Grid2 gene encoding the delta-2 excitatory amino acid receptor.

PubMed

Lalonde, R; Hayzoun, K; Selimi, F; Mariani, J; Strazielle, C

2003-11-01

Grid2(ho/ho) is a loss of function gene mutation resulting in abnormal dendritic arborizations of Purkinje cells. These mutants were compared in a series of motor coordination tests requiring balance and equilibrium to nonataxic controls (Grid2(ho/+)) and to a double mutant (Grid2(ho/Lc)) with an inserted Lc mutation. The performance of Grid2(ho/ho) mutant mice was poorer than that of controls on stationary beam, coat hanger, unsteady platform, and rotorod tests. Grid2(ho/Lc) did not differ from Grid2(Lc/+) mice. However, the insertion of the Lc mutation in Grid2(ho/Lc) potentiated the deficits found in Grid2(ho/ho) in stationary beam, unsteady platform, and rotorod tests. These results indicate a deleterious effect of the Lc mutation on Grid2-deficient mice.

Drug discrimination and neurochemical studies in alpha7 null mutant mice: tests for the role of nicotinic alpha7 receptors in dopamine release.

PubMed

Quarta, Davide; Naylor, Christopher G; Barik, Jacques; Fernandes, Cathy; Wonnacott, Susan; Stolerman, Ian P

2009-04-01

The nicotine discriminative stimulus has been linked to beta2-containing (beta2*) nicotinic receptors, with little evidence of a role for alpha7 nicotinic receptors, because nicotine discrimination was very weak in beta2 null mutant mice but normal in alpha7 mutants. As both alpha7 and beta2* nicotinic receptors have been implicated in nicotine-stimulated dopamine overflow, this study focused on the dopamine-mediated element in the nicotine stimulus by examining cross-generalisation between amphetamine and nicotine. Male alpha7 nicotinic receptor null mutant mice and wild-type controls were bred in-house and trained to discriminate nicotine (0.8 mg/kg) or (+)-amphetamine (0.6 mg/kg) from saline in a two-lever procedure with a tandem VI-30 FR-10 schedule of food reinforcement. Dopamine release from striatal slices was determined in parallel experiments. An alpha7 nicotinic receptor-mediated component of dopamine release was demonstrated in tissue from wild-type mice using choline as a selective agonist. This response was absent in tissue from null mutant animals. The mutation did not influence acquisition of drug discriminations but subtly affected the results of cross-generalisation tests. In mice trained to discriminate nicotine or amphetamine, there was partial cross-generalisation in wild-type mice and, at certain doses, these effects were attenuated in mutants. Further support for an alpha7 nicotinic receptor-mediated component was provided by the ability of the alpha7 nicotinic receptor antagonist methyllycaconitine to attenuate responses to nicotine and amphetamine in wild-type mice. These findings support the concept of an alpha7 nicotinic receptor-mediated dopaminergic element in nicotine discrimination, warranting further tests with selective dopamine agonists.

Testing the mutant selection window hypothesis with Escherichia coli exposed to levofloxacin in a rabbit tissue cage infection model.

PubMed

Ni, W; Song, X; Cui, J

2014-03-01

The purpose of this study was to test the mutant selection window (MSW) hypothesis with Escherichia coli exposed to levofloxacin in a rabbit model and to compare in vivo and in vitro exposure thresholds that restrict the selection of fluoroquinolone-resistant mutants. Local infection with E. coli was established in rabbits, and the infected animals were treated orally with various doses of levofloxacin once a day for five consecutive days. Changes in levofloxacin concentration and levofloxacin susceptibility were monitored at the site of infection. The MICs of E. coli increased when levofloxacin concentrations at the site of infection fluctuated between the lower and upper boundaries of the MSW, defined in vitro as the minimum inhibitory concentration (MIC99) and the mutant prevention concentration (MPC), respectively. The pharmacodynamic thresholds at which resistant mutants are not selected in vivo was estimated as AUC24/MPC > 20 h or AUC24/MIC > 60 h, where AUC24 is the area under the drug concentration time curve in a 24-h interval. Our finding demonstrated that the MSW existed in vivo. The AUC24/MPC ratio that prevented resistant mutants from being selected estimated in vivo is consistent with that observed in vitro, indicating it might be a reliable index for guiding the optimization of antimicrobial treatment regimens for suppression of the selection of antimicrobial resistance.

Color constancy of color-deficient observers under illuminations defined by individual color discrimination ellipsoids.

PubMed

Ma, Ruiqing; Kawamoto, Ken-Ichiro; Shinomori, Keizo

2016-03-01

We explored the color constancy mechanisms of color-deficient observers under red, green, blue, and yellow illuminations. The red and green illuminations were defined individually by the longer axis of the color discrimination ellipsoid measured by the Cambridge Colour Test. Four dichromats (3 protanopes and 1 deuteranope), two anomalous trichromats (2 deuteranomalous observers), and five color-normal observers were asked to complete the color constancy task by making a simultaneous paper match under asymmetrical illuminations in haploscopic view on a monitor. The von Kries adaptation model was applied to estimate the cone responses. The model fits showed that for all color-deficient observers under all illuminations, the adjustment of the S-cone response or blue-yellow chromatically opponent responses modeled with the simple assumption of cone deletion in a certain type (S-M, S-L or S-(L+M)) was consistent with the principle of the von Kries model. The degree of adaptation was similar to that of color-normal observers. The results indicate that the color constancy of color-deficient observers is mediated by the simplified blue-yellow color system with a von Kries-type adaptation effect, even in the case of brightness match, as well as by a possible cone-level adaptation to the S-cone when the illumination produces a strong S-cone stimulation, such as blue illumination.

Modeling of stress distributions on the microstructural level in Alloy 600

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kozaczek, K.J.; Petrovic, B.G.; Ruud, C.O.

1995-04-01

Stress distribution in a random polycrystalline material (Alloy 600) was studied using a topologically correct microstructural model. Distributions of von Mises and hydrostatic stresses at the grain vertices, which could be important in intergranular stress corrosion cracking, were analyzed as functions of microstructure, grain orientations and loading conditions. Grain size, shape, and orientation had a more pronounced effect on stress distribution than loading conditions. At grain vertices the stress concentration factor was higher for hydrostatic stress (1.7) than for von Mises stress (1.5). The stress/strain distribution in the volume (grain interiors) is a normal distribution and does not depend onmore » the location of the studied material volume i.e., surface vs/bulk. The analysis of stress distribution in the volume showed the von Mises stress concentration of 1.75 and stress concentration of 2.2 for the hydrostatic pressure. The observed stress concentration is high enough to cause localized plastic microdeformation, even when the polycrystalline aggregate is in the macroscopic elastic regime. Modeling of stresses and strains in polycrystalline materials can identify the microstructures (grain size distributions, texture) intrinsically susceptible to stress/strain concentrations and justify the correctness of applied stress state during the stress corrosion cracking tests. Also, it supplies the information necessary to formulate the local failure criteria and interpret of nondestructive stress measurements.« less

Functional census of mutation sequence spaces: The example of p53 cancer rescue mutants

PubMed Central

Danziger, Samuel A.; Swamidass, S. Joshua; Zeng, Jue; Dearth, Lawrence R.; Lu, Qiang; Chen, Jonathan H.; Cheng, Jainlin; Hoang, Vinh P.; Saigo, Hiroto; Luo, Ray; Baldi, Pierre; Brachmann, Rainer K.; Lathrop, Richard H.

2009-01-01

Many biomedical problems relate to mutant functional properties across a sequence space of interest, e.g., flu, cancer, and HIV. Detailed knowledge of mutant properties and function improves medical treatment and prevention. A functional census of p53 cancer rescue mutants would aid the search for cancer treatments from p53 rescue. We devised a general methodology for conducting a functional census of a mutation sequence space, and conducted a double-blind predictive test on the functional rescue property of 71 novel putative p53 cancer rescue mutants iteratively predicted in sets of 3. Double-blind predictive accuracy (15-point moving window) rose from 47% to 86% over the trial (r = 0.74). Code and data are available upon request1. PMID:17048398

Vesicular monoamine transporter 2 (Vmat2) knockdown elicits anxiety-like behavior in zebrafish.

PubMed

Wang, Yali; Li, Siyue; Liu, Wenwen; Wang, Fen; Hu, Li-Fang; Zhong, Zhao-Min; Wang, Han; Liu, Chun-Feng

2016-02-19

Vesicular monoamine transporter 2 (Vmat2) is widely distributed in the central nervous system, and responsible for uptaking transmitters into the vesicles. However, whether Vmat2-deficiency is related to the anxiety is rarely investigated, especially in zebrafish. Here, we reported Vmat2 heterzygous mutant zebrafish displayed anxiety-like behavior. The mutants spent less time in the top area and took longer latency to the top in the novel tank test. Consistently, they showed dark avoidance in the light/dark box test, with longer duration in the light zone and increased number of crossing between the two zones. Monoamine concentration analysis showed that the levels of monoamine neurotransmitters including dopamine (DA), 5-hydroxy tryptamine (5-HT) and norepinephrine (NE), as well as their metabolites were decreased in VMAT mutants. Taken together, these findings suggest that Vmat2 heterzygous mutant zebrafish may serve as a new model of anxiety, which may be related with the low level of DA, 5-HT and NE. Copyright © 2016 Elsevier Inc. All rights reserved.

Production of Trichoderma strains with pesticide-polyresistance by mutagenesis and protoplast fusion.

PubMed

Hatvani, Lóránt; Manczinger, László; Kredics, László; Szekeres, András; Antal, Zsuzsanna; Vágvölgyi, Csaba

2006-01-01

The sensitivity of two cold-tolerant Trichoderma strains belonging to the species T. harzianum and T. atroviride was determined to a series of pesticides widely used in agriculture. From the 16 pesticides tested, seven fungicides: copper sulfate, carbendazim, mancozeb, tebuconazole, imazalil, captan and thiram inhibited colony growth of the test strains significantly with minimal inhibitory concentrations of 300, 0.4, 50, 100, 100, 100 and 50 microg/ml, respectively. Mutants resistant to carbendazim and tebuconazole were produced from both wild type strains by means of UV-mutagenesis. The cross-resistance capabilities and in vitro antagonistic properties of the mutants were determined. Carbendazim-resistant mutants showed total cross-resistance to benomyl and thiabendazole at a concentration of 20 microg/ml. Intraspecific protoplast fusion was carried out between carbendazim- and tebuconazole-resistant mutants of both parental strains, and putative haploid recombinants with stable resistance to both pesticides were produced in the case of T. atroviride. These pesticide-polyresistant progenies are potential candidates for application in an integrated pest management system.

Comparing Alternative Kernels for the Kernel Method of Test Equating: Gaussian, Logistic, and Uniform Kernels. Research Report. ETS RR-08-12

ERIC Educational Resources Information Center

Lee, Yi-Hsuan; von Davier, Alina A.

2008-01-01

The kernel equating method (von Davier, Holland, & Thayer, 2004) is based on a flexible family of equipercentile-like equating functions that use a Gaussian kernel to continuize the discrete score distributions. While the classical equipercentile, or percentile-rank, equating method carries out the continuization step by linear interpolation,…

Study of chromatic adaptation using memory color matches, Part I: neutral illuminants.

PubMed

Smet, Kevin A G; Zhai, Qiyan; Luo, Ming R; Hanselaer, Peter

2017-04-03

Twelve corresponding color data sets have been obtained using the long-term memory colors of familiar objects as target stimuli. Data were collected for familiar objects with neutral, red, yellow, green and blue hues under 4 approximately neutral illumination conditions on or near the blackbody locus. The advantages of the memory color matching method are discussed in light of other more traditional asymmetric matching techniques. Results were compared to eight corresponding color data sets available in literature. The corresponding color data was used to test several linear (von Kries, RLAB, etc.) and nonlinear (Hunt & Nayatani) chromatic adaptation transforms (CAT). It was found that a simple two-step von Kries, whereby the degree of adaptation D is optimized to minimize the DEu'v' prediction errors, outperformed all other tested models for both memory color and literature corresponding color sets, whereby prediction errors were lower for the memory color sets. The predictive errors were substantially smaller than the standard uncertainty on the average observer and were comparable to what are considered just-noticeable-differences in the CIE u'v' chromaticity diagram, supporting the use of memory color based internal references to study chromatic adaptation mechanisms.

[A Case of Von Hippel-Lindau Disease with Nonfunctioning Pancreatic Neuroendocrine Tumors Treated by Duodenum-Preserving Resection of the Head of the Pancreas and Spleen-Preserving Resection of the Tail of the Pancreas].

PubMed

Umehara, Yutaka; Umehara, Minoru; Tokura, Tomohisa; Yachi, Takafumi; Takahashi, Kenichi; Morita, Takayuki; Hakamada, Kenichi

2015-10-01

A 26-year-old woman presented to our department with a diagnosis of multiple nonfunctioning pancreatic neuroendocrine tumors. She had a family history of pheochromocytoma and a medical history of bilateral adrenalectomy for pheochromocytoma at the age of 25 years. During follow-up treatment for adrenal insufficiency after the surgery, highly enhanced tumors in the pancreas were detected on contrast-enhanced CT. Other examinations found that the patient did not satisfy the clinical criteria for von Hippel-Lindau (VHL) disease. Considering her age and risk of developing multiple heterotopic and heterochronous tumors, we performed a duodenum-preserving resection of the head of the pancreas and spleen-preserving resection of the tail of the pancreas with informed consent. The histopathological findings revealed that all of the tumors were NET G1. She underwent genetic testing postoperatively and was diagnosed with VHL disease. This diagnosis meant that we were able to create an optimal treatment plan for the patient. If a tumor predisposition syndrome is suspected, VHL disease should be borne in mind and genetic testing after genetic counseling should be duly considered.

Operational art in the Defense: The German Abwehrschlachten in 1918

DTIC Science & Technology

2012-05-17

2 Carl von Clausewitz, On War, Michael Howard und Peter Paret ed. and trans. (New Jersey: Princeton University Press, 1989...Siegismund, 1937), 74. 21 Jacob Jung , Max von Gallwitz (1852-1937) (Osnabrück: Biblio-Verlag, 1995), 93 & 97. 22 Erich Ludendorff, Meine...23 Jung , Max von Gallwitz (1852-1937), 5-7. 24 Ibid., 8-16. 25 Ibid.,17-23. 13 At the outbreak of the war, Gallwitz received command

Physik gestern und heute Von der Metallstange zum Hochenergielaser

NASA Astrophysics Data System (ADS)

Heering, Peter

2002-05-01

Im Mai 1752 wurde in Marly bei Paris auf Anregung des amerikanischen Forschers und Politikers Benjamin Franklin erstmals die elektrische Natur des Blitzes nachgewiesen. Damals beschrieb Franklin auch eine technische Vorrichtung, die als Schutz von Gebäuden vor Blitzschlägen dienen sollte: den Blitzableiter. Diese aus heutiger Sicht scheinbar triviale Vorrichtung wurde aber keineswegs unmittelbar akzeptiert. Und bis heute ist die Forschung zum Schutz von Einrichtungen vor Blitzschlägen nicht abgeschlossen.

Robuste Verzweigungserkennung von Gefäßen in CTA-Datensätzen zur modellbasierten Extraktion der Centerline

NASA Astrophysics Data System (ADS)

Beck, Thomas; Fritz, Dominik; Biermann, Christina; Dillmann, Rüdiger

Bei der Befundung und Visualisierung von Blutgefäßen ist deren Centerline von zentraler Bedeutung. Die Unterscheidung zwischen unverzweigten Abschnitten des Gefäßes und Verzweigungsbereichen ermöglicht den Einsatz spezialisierter und sehr effizienter Algorithmen zur modellbasierten Extraktion der Centerline. In diesem Artikel wird ein robustes Verfahren zur Verzweigungserkennung vorgestellt. Das Verfahren beruht auf einem Front-Propagation-Ansatz mit dynamisch angepassten Schwellwerten und einer anschließenden Clusteranalyse. Die vorgestellte Methode zur Verzweigungserkennung wurde als Komponente einer Architektur zur Extraktion der Centerline auf handannotierten Datensätzen getestet. Erste Ergebnisse sind sehr vielversprechend und ermöglichen auch bei pathologischen Gefäßen eine robuste Detektion von Gefäßverzweigungen.

Strömende Flüssigkeiten und Gase

NASA Astrophysics Data System (ADS)

Heintze, Joachim

Die Bemerkung über die Probleme eines allgemeingültigen Ansatzes, die wir zu Anfang von Kap. 1 machten, gilt in noch höherem Maße für die Mechanik von strömenden Flüssigkeiten; dort erreicht man sogar ziemlich rasch die Grenze der Leistungsfähigkeit der heutigen Mathematik, d. h. wir können zwar - ausgehend von den Newtonschen Gesetzen (Bd. I/3) - eine Differentialgleichung für die Strömung von Flüssigkeiten aufstellen, die sog. Navier-Stokes-Gleichung, es sind aber keine allgemein anwendbaren Lösungsverfahren für diese Gleichung bekannt. Ein Blick in die Natur und auf die vielfältigen Strömungsphänomene zeigt, dass diese Tatsache nicht verwunderlich ist.

Dr. Wernher Von Braun Memorial Dinner

NASA Image and Video Library

2017-10-26

The annual Dr. Wernher Von Braun Memorial Dinner was held at the U.S. Space and Rocket Center's Davidson Center on October 26, 2017 with Keynote speaker General John Hyten, Commander of U.S. Strategic Command. Emcee was Mark Larson of Mark Larson Media Services, Inc. Dr. Wernher Von Braun Memorial Scholarships were presented to 8 college students by the National Space Club. Educator of the Year was awarded to Tammy Thorpe; Community Service award was presented to Huntsville, Al. Mayor Tommy Battle. The Communications Award was presented to retired astronaut Dr. Mike Massimino. The Distinguished Science Award was presented to Dr. Martin Weisskopf. The Astronautics Engineer Award was presented to Douglas R. Cooke. The Dr. Wernher Von Braun Space Flight Trophy was presented to Robert Lightfoot.

Defective balancing ability and hyperactivity in the CLX (circling behavior linked to the X-chromosome) mutant rat.

PubMed

Fuji, Jun-ichiro; Tanabe, Hiroyuki; Fukuda, Ryo; Ooshima, Yojiro

2003-12-01

We have reported that the recently described circling behavior rat (CLX) is a hereditary mutant controlled by a single sex-linked recessive gene (gene symbol: clx). This mutant shows intermittent circle walking and/or running and head tossing with the neck twisted. The abnormal behavior begins to appear around weaning and continues throughout life. In the present study, behavioral tests were performed during the suckling and post-weaning periods and when the rats reached maturity, and the following peculiar abnormalities were revealed: (1) in the righting reflex test, the CLX young show a tendency to take a longer time to revert to normal posture; (2) in the negative geotaxis test, they had difficulty moving upward at 12 days of age; (3) in the air righting reflex test, they frequently fell on their backs or shoulders even after weaning; (4) almost none of the CLX rats showed nystagmus, which is invariably observed in normal rats after rotating stimulation, at 20 weeks of age; and (5) they showed hyperactivity in the open field test at the age of 5 or 6 weeks and a higher degree of locomotor activity in the home cage at the age of 7 and 15 weeks. These results suggest that CLX mutant rats may have some defect in vestibular function (balance sense) or abnormalities in an area of the central nervous system responsible for posture control, e.g., in the dopaminergic or GABAergic neurons.

The Klebsiella pneumoniae wabG Gene: Role in Biosynthesis of the Core Lipopolysaccharide and Virulence

PubMed Central

Izquierdo, Luis; Coderch, Núria; Piqué, Nuria; Bedini, Emiliano; Michela Corsaro, Maria; Merino, Susana; Fresno, Sandra; Tomás, Juan M.; Regué, Miguel

2003-01-01

To determine the function of the wabG gene in the biosynthesis of the core lipopolysaccharide (LPS) of Klebsiella pneumoniae, we constructed wabG nonpolar mutants. Data obtained from the comparative chemical and structural analysis of LPS samples obtained from the wild type, the mutant strain, and the complemented mutant demonstrated that the wabG gene is involved in attachment to α-l-glycero-d-manno-heptopyranose II (l,d-HeppII) at the O-3 position of an α-d-galactopyranosyluronic acid (α-d-GalAp) residue. K. pneumoniae nonpolar wabG mutants were devoid of the cell-attached capsular polysaccharide but were still able to produce capsular polysaccharide. Similar results were obtained with K. pneumoniae nonpolar waaC and waaF mutants, which produce shorter LPS core molecules than do wabG mutants. Other outer core K. pneumoniae nonpolar mutants in the waa gene cluster were encapsulated. K. pneumoniae waaC, waaF, and wabG mutants were avirulent when tested in different animal models. Furthermore, these mutants were more sensitive to some hydrophobic compounds than the wild-type strains. All these characteristics were rescued by reintroduction of the waaC, waaF, and wabG genes from K. pneumoniae. PMID:14645282

Analysis of in vivo correction of defined mismatches in the DNA mismatch repair mutants msh2, msh3 and msh6 of Saccharomyces cerevisiae.

PubMed

Lühr, B; Scheller, J; Meyer, P; Kramer, W

1998-02-01

We have analysed the correction of defined mismatches in wild-type and msh2, msh3, msh6 and msh3 msh6 mutants of Saccharomyces cerevisiae in two different yeast strain backgrounds by transformation with plasmid heteroduplex DNA constructs. Ten different base/base mismatches, two single-nucleotide loops and a 38-nucleotide loop were tested. Repair of all types of mismatches was severely impaired in msh2 and msh3 msh6 mutants. In msh6 mutants, repair efficiency of most base/base mismatches was reduced to a similar extent as in msh3 msh6 double mutants. G/T and A/C mismatches, however, displayed residual repair in msh6 mutants in one strain background, implying a role for Msh3p in recognition of base/base mismatches. Furthermore, the efficiency of repair of base/base mismatches was considerably reduced in msh3 mutants in one strain background, indicating a requirement for MSH3 for fully efficient mismatch correction. Also the efficiency of repair of the 38-nucleotide loop was reduced in msh3 mutants, and to a lesser extent in msh6 mutants. The single-nucleotide loop with an unpaired A was less efficiently repaired in msh3 mutants and that with an unpaired T was less efficiently corrected in msh6 mutants, indicating non-redundant functions for the two proteins in the recognition of single-nucleotide loops.

Isolation of parafluorophenylalanine-resistant mutants from HeLa cell cultures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yim, L.K.; Stuart, W.D.

This report describes a method to isolate temperature-conditional phenylalanine transport mutants from the transformed human cell line HeLa. Using ultraviolet light as a mutagenic agent and DL-parafluorophenylalanine (PFPA), a poisonous analogue of L-phenylalanine, as a selective agent, mutagenized cells were selected for survival in the presence of PFPA at a temperature of 39 degrees C. Survivors of the mutagenesis and selection procedures were removed from the culture dishes by trypsin and cloned at a temperature of 35 degrees C. Seven of these lines isolated demonstrated continued resistance to PFPA at 39 degrees C. These lines were tested for uptake ofmore » L-phenylalanine at an external concentration of 100 microM and for continued resistance to PFPA at two concentrations. Cells were tested at 35 and at 39 degrees C. The data were compared to those obtained for the parental HeLa cell line under identical conditions. The seven mutant cell lines demonstrated varying resistances to PFPA and varying levels of accumulation of L-phenylalanine when tested at 35 and 39 degrees C. Three mutant lines were additionally tested for L-phenylalanine tRNA charging levels and for transport of L-arginine. The lines had parental cell levels of tRNA charging and L-arginine transport which suggest that the induced genetic defect affects a specific L-phenylalanine transport system.« less

Biocompatibility and biomineralization assessment of bioceramic-, epoxy-, and calcium hydroxide-based sealers.

PubMed

Bueno, Carlos Roberto Emerenciano; Valentim, Diego; Marques, Vanessa Abreu Sanches; Gomes-Filho, João Eduardo; Cintra, Luciano Tavares Angelo; Jacinto, Rogério Castilho; Dezan-Junior, Eloi

2016-06-14

Obturation of the root canal system aims to fill empty spaces, promoting hermetic sealing and preventing bacterial activity in periapical tissues. This should provide optimal conditions for repair, stimulating the process of biomineralization. An endodontic sealer should be biocompatible once it is in direct contact with periapical tissues. The aim of this study was to evaluate the rat subcutaneous tissue response to implanted polyethylene tubes filled with Smartpaste Bio, Acroseal, and Sealapex and investigate mineralization ability of these endodontic sealers. Forty Wistar rats were assigned to the three sealers groups and control group, (n = 10 animals/group) and received subcutaneous implants containing the test sealers, and the control group were implanted with empty tubes. After days 7, 15, 30, and 60, animals were euthanized and polyethylene tubes were removed with the surrounding tissues. Inflammatory infiltrate and thickness of the fibrous capsule were histologically evaluated. Mineralization was analyzed by Von Kossa staining and polarized light. Data were tabulated and analyzed via Kruskal-Wallis and Dunn's test. All tested materials induced a moderate inflammatory reaction in the initial periods. Smartpaste Bio induced the mildest inflammatory reactions after day 15. No difference was observed among groups after days 30 or 60. Von Kossa-positive staining and birefringent structures observed under polarized light revealed a larger mineralization area in Sealapex-treated animals followed by Smartpaste Bio-treated animals. At the end of the experiment, all tested sealers were found to be biocompatible. All sealers induced biomineralization, except Acroseal, which induced a mild tissue reaction.

Hemophilia and von Willebrand's disease: 1. Diagnosis, comprehensive care and assessment. Association of Hemophilia Clinic Directors of Canada.

PubMed Central

1995-01-01

OBJECTIVE: To present current strategies for the assessment and comprehensive care of patients with hemophilia and von Willebrand's disease. OPTIONS: Hospital care, home care, single-provider care and multidisciplinary care. OUTCOMES: Morbidity and quality of life associated with bleeding and treatment. EVIDENCE: Relevant clinical studies and reports published from 1974 to 1994 were examined. A search was conducted of own reprint files, MEDLINE, citations in the articles reviewed and references provided by colleagues. In the MEDLINE search the following terms were used singly or in combination: "hemophilia," "von Willebrand's disease," "Factor VIII," "Factor IX," "von Willebrand factor," "diagnosis," "management," "home care," "comprehensive care," "inhibitor," "AIDS," "hepatitis," "life expectancy," "complications," "practice guidelines," "consensus statement" and "controlled trial." The in-depth review included only articles written in English from North America and Europe that were relevant to human disease and to a predetermined outline. The availability of treatment products in Canada was also considered. VALUES: Minimizing morbidity and maximizing functional status and quality of life were given a high value. BENEFITS, HARMS AND COSTS: The optimal use of treatment procedures and home care offers patients the advantages of minimized disability, improved survival and financial benefit. It is also cost effective. Potential harm, including the risk of hepatitis B, hepatitis C and HIV infection, has now been minimized through viral inactivation of plasma-derived coagulation-factor concentrates and through the use of recombinant clotting factor concentrates and other non-plasma-derived hemostatic agents. RECOMMENDATIONS: Patients with hemophilia and severe von Willebrand's disease should be followed in comprehensive care centres that offer expertise in the diagnosis, assessment and management of bleeding and complications and that can meet the educational and counselling needs of patients, family members and health care providers. Eligible patients should be enrolled in a home self-infusion program. Patients with hemophilia and von Willebrand's disease should wear or carry Medic Alert identification. They should be vaccinated against hepatitis B and attend for routine follow-up examinations. Laboratory testing should be carried out as required, and dental and surgical care should be undertaken in consultation with a hematologist. VALIDATION: These recommendations were reviewed and approved by the Association of Hemophilia Clinic Directors of Canada (AHCDC) and the Medical and Scientific Advisory Committee of the Canadian Hemophilia Society. No similar consensus statements or practice guidelines are available for comparison. SPONSORS: These recommendations were developed at the request of the Canadian Blood Agency, which funds the provision of all coagulation-factor concentrates for people with congenital bleeding disorders, and were developed and endorsed by the AHCDC and the Medical and Scientific Advisory Committee of the Canadian Hemophilia Society. PMID:7796372

Big Biology: Supersizing Science During the Emergence of the 21st Century

PubMed Central

Vermeulen, Niki

2017-01-01

Ist Biologie das jüngste Mitglied in der Familie von Big Science? Die vermehrte Zusammenarbeit in der biologischen Forschung wurde in der Folge des Human Genome Project zwar zum Gegenstand hitziger Diskussionen, aber Debatten und Reflexionen blieben meist im Polemischen verhaftet und zeigten eine begrenzte Wertschätzung für die Vielfalt und Erklärungskraft des Konzepts von Big Science. Zur gleichen Zeit haben Wissenschafts- und Technikforscher/innen in ihren Beschreibungen des Wandels der Forschungslandschaft die Verwendung des Begriffs Big Science gemieden. Dieser interdisziplinäre Artikel kombiniert eine begriffliche Analyse des Konzepts von Big Science mit unterschiedlichen Daten und Ideen aus einer Multimethodenuntersuchung mehrerer großer Forschungsprojekte in der Biologie. Ziel ist es, ein empirisch fundiertes, nuanciertes und analytisch nützliches Verständnis von Big Biology zu entwickeln und die normativen Debatten mit ihren einfachen Dichotomien und rhetorischen Positionen hinter sich zu lassen. Zwar kann das Konzept von Big Science als eine Mode in der Wissenschaftspolitik gesehen werden – inzwischen vielleicht sogar als ein altmodisches Konzept –, doch lautet meine innovative Argumentation, dass dessen analytische Verwendung unsere Aufmerksamkeit auf die Ausweitung der Zusammenarbeit in den Biowissenschaften lenkt. Die Analyse von Big Biology zeigt Unterschiede zu Big Physics und anderen Formen von Big Science, namentlich in den Mustern der Forschungsorganisation, der verwendeten Technologien und der gesellschaftlichen Zusammenhänge, in denen sie tätig ist. So können Reflexionen über Big Science, Big Biology und ihre Beziehungen zur Wissensproduktion die jüngsten Behauptungen über grundlegende Veränderungen in der Life Science-Forschung in einen historischen Kontext stellen. PMID:27215209

Wernher von Braun with German Officers and Others

NASA Technical Reports Server (NTRS)

1942-01-01

General Erich Fellgiebel, head of the German Army Information Service during World War II, congratulates members of the von Braun rocket team from Peenemunde for their October 3, 1942 A4 flight. Pictured front center is General Erich Fellgiebel. Shaking hands are General Walter Dornberger (left) and General Janssen, commanding officer of Peenemuende with Rudolph Hermarn to their right. Picture left to right in the back row are Wernher von Braun, Captain Stoelzel, Luftwaffe, and Dr. Gerhard Reisig.

Umgang mit Gedichten: Bemerkungen zu funf Gedichten von Johann Wolfgang von Goethe (Dealing with Poetry: Observations on Five Poems by Johann Wolfgang von Goethe).

ERIC Educational Resources Information Center

Nethersole, Reingard

1972-01-01

The lyric poem is the most concentrated form of literary communication. The formulation of an approach to interpretation can be a useful tool for the instructor. The poem to be interpreted should be examined in six aspects: (1) information provided in the title, (2) the sound of the poem as read aloud, (3) the clear understanding of the meaning of…

Exploiting Remotely Piloted Aircraft: Understanding the Impact of Strategy on the Approach to Autonomy

DTIC Science & Technology

2011-06-01

Werner Von Braun acted to ensure that his rocket team sought capture by the U.S. Army rather than the Soviets. His team became the nucleus of...technically superior and well- envisioned air force capabilities to counter an emerging threat. Colonel General Von Seeckt established a forum to...KS.: University Press of Kansas, 1997), 51-52. Von Seeckt held the rank of Colonel General, the highest rank of the German military. 15 James

Project Apollo Lights the Way for Acquisition Success

DTIC Science & Technology

2009-10-01

Marshall Space Flight Center Dr. Werner von Braun and NASA engi- neers and scientists knew they wanted to be able to explore the lunar surface...work was similar to what we in DoD now refer to as a capabilities-based assessment. Von Braun and his staff were convinced of the practicality of the...gineers demonstrated an ingenious prototype to von Braun , NASA decided to proceed once more with developments for a Lunar Rover. In a classic example of

Comparing Theory and Practice: An Application of Complexity Theory to General Ridgway’s Success in Korea

DTIC Science & Technology

2010-12-02

Theory Defined 48 Doctrine 48 Interwar Doctrine a Historical Perspective 52 Adaptive Campaigning 53 Carl von Clausewitz 53 Comparative Analysis of...order effects that may be traced through an understanding of the environment. Carl von Clausewitz suggested using history as a tool, to provide a lens...Cworks/Works.htm (accessed 10/2, 2010). 6 Carl von Clausewitz, On War, trans. Ed. Michael Howard and Peter Paret (Princeton: Princeton University

Bewertung von Fahrzeuggeräuschen

NASA Astrophysics Data System (ADS)

Genuit, Klaus; Schulte-Fortkamp, Brigitte; Fiebig, André; Haverkamp, Michael

Bei der Wahrnehmung und Beurteilung eines Automobils sind unzählige Merkmale und Eigenschaften von Bedeutung. Dabei können Merkmale objektiv-technisch beschrieben werden, wie Angaben zur Motorisierung, Höchstgeschwindigkeit, Drehmoment, zulässige Zuladung, Verbrauch usw. Daneben sind weitere Eigenschaften von Bedeutung, die sich einer einfachen objektiv-technischen Beschreibung entziehen. Hier sind Begriffe zu nennen, wie Sicherheit, allgemeine Qualitätsanmutung, Design, Ergonomie, Komfort, Haptik, Fahrdynamik, Zuverlässigkeit, die deutlich schwieriger objektiv erfassbar und beschreibbar sind (Abb. 4.1).

Wirksamkeit und Sicherheit von Fumarsäureestern in Kombination mit Phototherapie bei Patienten mit moderater bis schwerer Plaque-Psoriasis (FAST).

PubMed

Weisenseel, Peter; Reich, Kristian; Griemberg, Wiebke; Merten, Katharina; Gröschel, Christine; Gomez, Natalie Nunez; Taipale, Kirsi; Bräu, Beate; Zschocke, Ina

2017-02-01

Die Behandlung von Psoriasis-Patienten mit einer Kombination aus Fumarsäureestern (FSE, Fumaderm ® ) und Phototherapie (UV) ist verbreitet, wurde aber im Rahmen von Studien wenig untersucht. Bisher liegen lediglich Daten aus einer kleinen Pilotstudie vor. Intention dieser Studie war, eine FSE/UV-Kombinationsbehandlung an einem größeren Patientenkollektiv mit mittelschwerer bis schwerer Psoriasis zu untersuchen. In dieser prospektiven, multizentrischen, nichtinterventionellen Studie wurden Daten von Patienten mit FSE/UV-Kombinationstherapie hinsichtlich der Wirksamkeit (PGA' PASI, DLQI, EQ-5D), Sicherheit und Dosierung über einen Zeitraum von zwölf Monaten erfasst und mit Daten einer retrospektiven Studie mit FSE-Monotherapie verglichen. Es wurden Daten von 363 Patienten ausgewertet. Unter der Kombinationstherapie verbesserten sich alle Wirksamkeitsparameter deutlich. Im Vergleich zur Monotherapie mit FSE konnte durch die Kombination mit UV ein schnellerer Wirkeintritt erzielt werden, wobei nach zwölf Monaten kein Unterschied in der Wirksamkeit bestand. Die Dauer und Art der Phototherapie zeigte keinen Einfluss auf die Wirksamkeitsparameter. Allgemein wurde die Kombinationstherapie gut vertragen. Unerwünschte Ereignisse wurden bei 7 % der Patienten berichtet. Die FSE/UV Kombinationstherapie zeigt eine gute Wirksamkeit und Verträglichkeit und kann zu einem schnelleren Wirkeintritt führen. Eine Kombinationstherapie erscheint vor allem in den ersten drei Monaten der FSE Behandlung sinnvoll. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

von Braun and German Publisher

NASA Technical Reports Server (NTRS)

1969-01-01

In this photograph, Guenter Ogger of Capitol Magazine, West Germany, greets Marshall Space Flight Center Director, Dr. Wernher von Braun. Mr. Ogger interviewed the famous rocket scientist for his magazine.

Aufbau und Belastung tribologischer Systeme

NASA Astrophysics Data System (ADS)

Schumacher, Jan; Murrenhoff, Hubertus

Die Tribologie ist laut DIN 50323 die Wissenschaft und Technik von aufeinander einwirkenden Oberflächen in Relativbewegung. Es werden die Teilgebiete Reibung, Verschleiß und Schmierung von ihr behandelt.

A method for probing the mutational landscape of amyloid structure.

PubMed

O'Donnell, Charles W; Waldispühl, Jérôme; Lis, Mieszko; Halfmann, Randal; Devadas, Srinivas; Lindquist, Susan; Berger, Bonnie

2011-07-01

Proteins of all kinds can self-assemble into highly ordered β-sheet aggregates known as amyloid fibrils, important both biologically and clinically. However, the specific molecular structure of a fibril can vary dramatically depending on sequence and environmental conditions, and mutations can drastically alter amyloid function and pathogenicity. Experimental structure determination has proven extremely difficult with only a handful of NMR-based models proposed, suggesting a need for computational methods. We present AmyloidMutants, a statistical mechanics approach for de novo prediction and analysis of wild-type and mutant amyloid structures. Based on the premise of protein mutational landscapes, AmyloidMutants energetically quantifies the effects of sequence mutation on fibril conformation and stability. Tested on non-mutant, full-length amyloid structures with known chemical shift data, AmyloidMutants offers roughly 2-fold improvement in prediction accuracy over existing tools. Moreover, AmyloidMutants is the only method to predict complete super-secondary structures, enabling accurate discrimination of topologically dissimilar amyloid conformations that correspond to the same sequence locations. Applied to mutant prediction, AmyloidMutants identifies a global conformational switch between Aβ and its highly-toxic 'Iowa' mutant in agreement with a recent experimental model based on partial chemical shift data. Predictions on mutant, yeast-toxic strains of HET-s suggest similar alternate folds. When applied to HET-s and a HET-s mutant with core asparagines replaced by glutamines (both highly amyloidogenic chemically similar residues abundant in many amyloids), AmyloidMutants surprisingly predicts a greatly reduced capacity of the glutamine mutant to form amyloid. We confirm this finding by conducting mutagenesis experiments. Our tool is publically available on the web at http://amyloid.csail.mit.edu/. lindquist_admin@wi.mit.edu; bab@csail.mit.edu.

Aktuelle Entwicklungen - Orthopädische Implantate

NASA Astrophysics Data System (ADS)

Riner, Marc A.

Die guten Resultate und langen Standzeiten von bis zu 15 und 20 Jahren von implantierten Hüftendoprothesen führen dazu, immer jüngere Patienten mit einem Hüftgelenkersatz zu behandeln. Die Versorgung von jungen aktiven Patienten mit einer Hüftendoprothese stellt jedoch eine besondere Herausforderung dar [1]. Trotz umfangreicher Materialentwicklungen, Designoptimierungen und Verbesserungen der Operationstechnik, haben sich die Standzeiten der Prothesen zwar wesentlich verbessert, ist jedoch bei jungen Patienten verglichen mit denen von älteren Patienten deutlich verkürzt [2, 3]. Zudem kann die Hüftprothesenverankerung durch Knochenresektion im Rahmen der Erstimplantation, Adaptionsvorgängen im Knochen (stress shielding) aufgrund unphysiologischer Krafteinleitung, abriebbedingte Osteolyse und während der Implantat- bzw. Knochenzemententfernung auftretende knöcherne Defekte zu unbefriedigende Reimplantationsbedingungen im Fall einer Revision führen [4]. Dies hat in jüngerer Zeit zur Entwicklung von verschiedenen Endoprothesensystemen mit einem möglichst geringen Knochenverlust und damit einhergehenden verbesserten Rückzugsmöglichkeit im Revisionsfall geführt. Bei den knochensparend verankerten Hüftprothesen werden allgemein zwei Typen, die Schenkelhalsprothese und der Oberflächenersatz, unterschieden.

Zuverlässigkeit digitaler Schaltungen unter Einfluss von intrinsischem Rauschen

NASA Astrophysics Data System (ADS)

Kleeberger, V. B.; Schlichtmann, U.

2011-08-01

Die kontinuierlich fortschreitende Miniaturisierung in integrierten Schaltungen führt zu einem Anstieg des intrinsischen Rauschens. Um den Einfluss von intrinsischem Rauschen auf die Zuverlässigkeit zukünftiger digitaler Schaltungen analysieren zu können, werden Methoden benötigt, die auf CAD-Verfahren wie Analogsimulation statt auf abschätzenden Berechnungen beruhen. Dieser Beitrag stellt eine neue Methode vor, die den Einfluss von intrinsischem Rauschen in digitalen Schaltungen für eine gegebene Prozesstechnologie analysieren kann. Die Amplituden von thermischen, 1/f und Schrotrauschen werden mit Hilfe eines SPICE Simulators bestimmt. Anschließend wird der Einfluss des Rauschens auf die Schaltungszuverlässigkeit durch Simulation analysiert. Zusätzlich zur Analyse werden Möglichkeiten aufgezeigt, wie die durch Rauschen hervorgerufenen Effekte im Schaltungsentwurf mit berücksichtigt werden können. Im Gegensatz zum Stand der Technik kann die vorgestellte Methode auf beliebige Logikimplementierungen und Prozesstechnologien angewendet werden. Zusätzlich wird gezeigt, dass bisherige Ansätze den Einfluss von Rauschen bis um das Vierfache überschätzen.

Physical Realization of von Neumann Lattices in Rotating Bose Gases with Dipole Interatomic Interactions.

PubMed

Cheng, Szu-Cheng; Jheng, Shih-Da

2016-08-22

This paper reports a novel type of vortex lattice, referred to as a bubble crystal, which was discovered in rapidly rotating Bose gases with long-range interactions. Bubble crystals differ from vortex lattices which possess a single quantum flux per unit cell, while atoms in bubble crystals are clustered periodically and surrounded by vortices. No existing model is able to describe the vortex structure of bubble crystals; however, we identified a mathematical lattice, which is a subset of coherent states and exists periodically in the physical space. This lattice is called a von Neumann lattice, and when it possesses a single vortex per unit cell, it presents the same geometrical structure as an Abrikosov lattice. In this report, we extend the von Neumann lattice to one with an integral number of flux quanta per unit cell and demonstrate that von Neumann lattices well reproduce the translational properties of bubble crystals. Numerical simulations confirm that, as a generalized vortex, a von Neumann lattice can be physically realized using vortex lattices in rapidly rotating Bose gases with dipole interatomic interactions.

Qualitätsmanagement in molekularbiologischen Laboratorien

NASA Astrophysics Data System (ADS)

Schulze, Manuela

Jedes Laboratorium führt Untersuchungen nach bestem Wissen und Gewissen durch, und jeder Analytiker weiß von sich, dass er/sie gute Arbeit macht. Trotzdem können Analysen des gleichen Probenmaterials in verschiedenen Laboren zu unterschiedlichen Ergebnissen führen. Sofern es sich dabei nicht um Untersuchungen im Bereich der Nachweisgrenze und damit letztlich um statistisch bedingte Unterschiede oder Inhomogenitäten im Probenmaterial handelt, trägt dies nicht zur Vertrauenswürdigkeit von analytischen Untersuchungsergebnissen bei. Mit der zunehmenden Globalisierung der Märkte rückt die gegenseitige Anerkennung von analytischen Resultaten immer stärker in den Vordergrund. Die Vergleichbarkeit von Laborresultaten wird erleichtert, wenn sich die Laboratorien auf die gleichen Richtlinien zur Vorgehensweise und Handhabung ihrer Arbeiten verständigen. Im Bereich der Laboruntersuchungen von Lebensmitteln, Futtermitteln und Saatgut ist als derartige Rischt-Schnur die EN ISO/IEC 17025 [1] anerkannt. Diese Norm enthält alle Anforderungen, die Prüflaboratorien erfüllen müssen, wenn sie nachweisen wollen, dass sie ein Qualitätsmanagementsystem betreiben, technisch (meint: fachlich) kompetent und fähig sind, fachlich fundierte Ergebnisse zu erzielen.

Darwinische Kulturtheorie - Evolutionistische und "evolutionistische`` Theorien sozialen Wandels

NASA Astrophysics Data System (ADS)

Antweiler, Christoph

Evolutionistische Argumentationen außerhalb der Biologie sind weit verbreitet. Wenn sie vertreten werden, heißt das mitnichten, dass sie notwendigerweise von darwinischen Argumenten geprägt sind. Wenn man Evolution und Kultur aus explizit darwinischer Perspektive zusammen bringt, bedeutet das noch lange nicht unbedingt Soziobiologie. Und es bedeutet sicherlich nicht Sozialdarwinismus. Dieser Beitrag soll einen Überblick der so genannten evolutionären Ansätze bzw. evolutionistischen Ansätze zu menschlichen Gesellschaften bzw. Kulturen geben. Es soll gezeigt werden, was in den Ansätzen analytisch zu trennen ist und was synthetisch zusammen gehört. Mein Beitrag ist nicht wissenschaftsgeschichtlich angelegt, sondern systematisch ausgerichtet und hat zwei Schwerpunkte (Antweiler 2008; Antweiler 2009b). Zum einen geht es um kausale Zusammenhänge von organischer Evolution und gesellschaftlichem Wandel. Auf der anderen Seite werden Analogien zwischen biotischer und kultureller Evolution erläutert, die als spezifische Ähnlichkeiten dieser beiden als grundsätzlich verschieden gesehenen Prozesse aufgefasst werden. Dadurch wird die Frage aufgeworfen, ob die Evolution von Organismen einerseits und die Transformation von Gesellschaften bzw. Kulturen andererseits, spezielle Fälle eines allgemeinen Modells von Evolution darstellen.

Rice LGD1 containing RNA binding activity affects growth and development through alternative promoters.

PubMed

Thangasamy, Saminathan; Chen, Pei-Wei; Lai, Ming-Hsing; Chen, Jychian; Jauh, Guang-Yuh

2012-07-01

Tiller initiation and panicle development are important agronomical traits for grain production in Oryza sativa L. (rice), but their regulatory mechanisms are not yet fully understood. In this study, T-DNA mutant and RNAi transgenic approaches were used to functionally characterize a unique rice gene, LAGGING GROWTH AND DEVELOPMENT 1 (LGD1). The lgd1 mutant showed slow growth, reduced tiller number and plant height, altered panicle architecture and reduced grain yield. The fewer unelongated internodes and cells in lgd1 led to respective reductions in tiller number and to semi-dwarfism. Several independent LGD1-RNAi lines exhibited defective phenotypes similar to those observed in lgd1. Interestingly, LGD1 encodes multiple transcripts with different transcription start sites (TSSs), which were validated by RNA ligase-mediated rapid amplification of 5' and 3' cDNA ends (RLM-RACE). Additionally, GUS assays and a luciferase promoter assay confirmed the promoter activities of LGD1.1 and LGD1.5. LGD1 encoding a von Willebrand factor type A (vWA) domain containing protein is a single gene in rice that is seemingly specific to grasses. GFP-tagged LGD1 isoforms were predominantly detected in the nucleus, and weakly in the cytoplasm. In vitro northwestern analysis showed the RNA-binding activity of the recombinant C-terminal LGD1 protein. Our results demonstrated that LGD1 pleiotropically regulated rice vegetative growth and development through both the distinct spatiotemporal expression patterns of its multiple transcripts and RNA binding activity. Hence, the study of LGD1 will strengthen our understanding of the molecular basis of the multiple transcripts, and their corresponding polypeptides with RNA binding activity, that regulate pleiotropic effects in rice. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

Determination of the termination efficiency of the transcription terminator using different fluorescent profiles in green fluorescent protein mutants.

PubMed

Nojima, Takahiko; Lin, Angela C; Fujii, Teruo; Endo, Isao

2005-12-01

An approach in determining the intrinsic termination efficiency (%T) of transcription termination using green fluorescent protein (GFP) mutants was developed. This approach utilizes a cassette vector in which the tested terminator is introduced between two GFP mutant genes: an ultraviolet-optimized mutant (GFPuv: F99S, M153T, V163A) and a blue-shifted mutant (BFP: F64L, S65T, T145F). The ratio of the fluorescence intensity of BFP to GFPuv after transcription and translation represents the termination efficiency of the terminator. E. coli ribosomal RNA operon T1 terminator, phage lambda terminator site R2, E. coli tryptophane attenuater were introduced into the vector, and their transcriptional efficiencies were estimated as 89, 79, and 24%, respectively, showing good agreement with published data.

Wernher von Braun

NASA Image and Video Library

1962-12-20

Dr. von Braun, Major General Francis McMorrow, and Alabama Governor, John Patterson (far left) participated in the ground breaking ceremony for the University of Alabama Research Institute in Huntsville, December 20, 1962.

Wernher von Braun

NASA Image and Video Library

1965-11-05

In this photograph, Marshall Space Flight Center Director, Dr. Wernher von Braun, presents a Co-Inventor’s award to MSFC employee Martin Hall of the Mechanical Engineering Laboratory during the NASA Anniversary ceremony.

Wt1 dictates the fate of fetal and adult Leydig cells during development in the mouse testis.

PubMed

Wen, Qing; Zheng, Qiao-Song; Li, Xi-Xia; Hu, Zhao-Yuan; Gao, Fei; Cheng, C Yan; Liu, Yi-Xun

2014-12-15

Wilms' tumor 1 (Wt1) is a tumor suppressor gene encoding ∼24 zinc finger transcription factors. In the mammalian testis, Wt1 is expressed mostly by Sertoli cells (SCs) involved in testis development, spermatogenesis, and adult Leydig cell (ALC) steroidogenesis. Global knockout (KO) of Wt1 is lethal in mice due to defects in embryogenesis. Herein, we showed that Wt1 is involved in regulating fetal Leydig cell (FLC) degeneration and ALC differentiation during testicular development. Using Wt1(-/flox);Amh-Cre mice that specifically deleted Wt1 in the SC vs. age-matched wild-type (WT) controls, FLC-like-clusters were found in Wt1-deficient testes that remained mitotically active from postnatal day 1 (P1) to P56, and no ALC was detected at these ages. Leydig cells in mutant adult testes displayed morphological features of FLC. Also, FLC-like cells in adult mutant testes had reduced expression in ALC-associated genes Ptgds, Sult1e1, Vcam1, Hsd11b1, Hsd3b6, and Hsd17b3 but high expression of FLC-associated genes Thbs2 and Hsd3b1. Whereas serum LH and testosterone level in mutant mice were not different from controls, intratesticular testosterone level was significantly reduced. Deletion of Wt1 gene also perturbed the expression of steroidogenic enzymes Star, P450c17, Hsd3b6, Hsd3b1, Hsd17b1, and Hsd17b3. FLCs in adult mutant testes failed to convert androstenedione to testosterone due to a lack of Hsd17b3, and this defect was rescued by coculturing with fetal SCs. In summary, FLC-like cells in mutant testes are putative FLCs that remain mitotically active in adult mice, illustrating that Wt1 dictates the fate of FLC and ALC during postnatal testis development. Copyright © 2014 the American Physiological Society.

[The original German scholarly literature of medieval falconry and the history of its scientific research].

PubMed

Giese, Martina

2007-01-01

German scholarly literature (Fachliteratur) of the middle ages devoted to falconry falls into two main categories: Translations, mostly of latin works, and original treatises. After a short survey of falconry in the past, this article will discuss the original treatises and the history of their analysis since the 19th century. In this context it will deal with the research of the following scholars: Joseph von Hammer-Purgstall, Anton von Perger, Ernst von Dombrowski, Hermann Werth, Christoph von Biedermann and--most importantly--Kurt Lindner. The appendix contains the editio princeps of the German Münchener Rezeptar I from the codex unicus, München, Universitätsbibliothek, 80 Cod. ms. 354, fol. 31r-33r (dating from the 15th century).

Werkstoffe

NASA Astrophysics Data System (ADS)

Hornbogen, Erhard; Eggeler, Gunther; Werner, Ewald

Lernziel: Dieses Kapitel vermittelt einen ersten Eindruck von Werkstoffen, die bestimmte technische Eigenschaften besitzen müssen, dabei einfach herstellbar sein sollen und die Forderung der Wirtschaftlichkeit erfüllen müssen. Wir diskutieren Werkstoffe in einfachen, allgemeinen und speziellen Zusammenhängen und lernen das Wissensgebiet Werkstoffkunde kennen, das die Werkstoffwissenschaft und die Werkstofftechnik umfasst. Wir verschaffen uns einen ersten Eindruck vom mikroskopischen Aufbau der vier Werkstoffgruppen Metalle, Gläser/Keramiken, Kunststoffe und Verbundwerkstoffe. Wir lernen einige wichtige Werkstoffeigenschaften kennen. Es geht dann um zuverl ässige Datenüber Eigenschaften von Werkstoffen und in diesem Zusammenhang wird die Prüfung, die Normung und die Bezeichnung von Werkstoffen betrachtet. Schließlich befassen wir uns kurz mit der zeitlichen Entwicklung von Werkstoffen und führen den Begriff der Nachhaltigkeit ein.

Gesellschaft, Lebensgemeinschaft, Ökosystem - Über die Kongruenz von politischen und ökologischen Theorien der Entwicklung

NASA Astrophysics Data System (ADS)

Voigt, Annette

Im Jahr 1859 veröffentlichte Charles Darwin "On the Origin of Species“. Seine Evolutionstheorie ist das wohl spektakulärste Beispiel einer naturwissenschaftlichen Theorie großer gesellschaftlicher Relevanz. Ihre verschiedenen Facetten wurden in der Öffentlichkeit kontrovers diskutiert, unter anderem auch ihre Anwendung zur Erklärung von Zuständen und Prozessen menschlicher Gesellschaften. Zum Teil wurde die Seiensweise der Natur - scheinbar unabhängig von gesellschaftlichen Interessen - für die Erklärung und Legitimation gesellschaftlicher Zustände oder die Legitimation von politischen Ideologien herangezogen (Sozialdarwinismus). Denn Gesellschaft funktioniere ja so, wie Darwin die Natur erklärt habe: es herrsche z. B. Konkurrenzkampf, Auslese und Arbeitsteilung, Erfolg hätten diejenigen, die sich an die Bedingungen am Besten anpassten.

S2k-Leitlinie zum Gebrauch von Präparationen zur lokalen Anwendung auf der Haut (Topika).

PubMed

Wohlrab, Johannes; Staubach, Petra; Augustin, Matthias; Eisert, Lisa; Hünerbein, Andreas; Nast, Alexander; Reimann, Holger; Strömer, Klaus; Mahler, Vera

2018-03-01

Diese Leitlinie richtet sich an Assistenz- und Fachärzte der Dermatologie sowie an Kostenträger und politische Entscheidungsgremien. Die Leitlinie wurde im formellen Konsensusverfahren (S2k) von Dermatologen unter Einbindung von Apothekern erstellt. Die Leitlinie stellt allgemeine Aspekte der Pharmakokinetik sowie der regulatorischen Begrifflichkeiten dar. Es werden Empfehlungen zur Indikation von Magistralrezepturen sowie deren Qualitätssicherung gegeben. Die Bedeutung der galenischen Grundlagen und die Problematik bei einer Substitution gegeneinander verschiedener Grundlagen werden dargestellt. Die Leitlinie umfasst Kriterien zur Auswahl einer adäquaten Grundlage sowie spezifische Aspekte zur Therapieplanung. Die Leitlinie gibt Empfehlungen zum Management bei Unverträglichkeiten gegenüber Bestandteilen der Grundlagen oder Hilfsstoffe. © 2018 The Authors | Journal compilation © Blackwell Verlag GmbH, Berlin.

Some Experiments with Respiratory Deficient Mutants of Yeast (Saccharomyces cerevisiae)

ERIC Educational Resources Information Center

Freeland, P. W.

1978-01-01

Methods are described for the induction and identification of respiratory deficient mutants in yeast. Practical schemes are given to enable students to obtain dose-response information for physical and chemical mutagens such as heat, ultraviolet light, or acriflavine. A simple test for environmental mutagens is described. (Author/MA)

Reversal of a full-length mutant huntingtin neuronal cell phenotype by chemical inhibitors of polyglutamine-mediated aggregation

PubMed Central

Wang, Jin; Gines, Silvia; MacDonald, Marcy E; Gusella, James F

2005-01-01

Background Huntington's disease (HD) is an inherited neurodegenerative disorder triggered by an expanded polyglutamine tract in huntingtin that is thought to confer a new conformational property on this large protein. The propensity of small amino-terminal fragments with mutant, but not wild-type, glutamine tracts to self-aggregate is consistent with an altered conformation but such fragments occur relatively late in the disease process in human patients and mouse models expressing full-length mutant protein. This suggests that the altered conformational property may act within the full-length mutant huntingtin to initially trigger pathogenesis. Indeed, genotype-phenotype studies in HD have defined genetic criteria for the disease initiating mechanism, and these are all fulfilled by phenotypes associated with expression of full-length mutant huntingtin, but not amino-terminal fragment, in mouse models. As the in vitro aggregation of amino-terminal mutant huntingtin fragment offers a ready assay to identify small compounds that interfere with the conformation of the polyglutamine tract, we have identified a number of aggregation inhibitors, and tested whether these are also capable of reversing a phenotype caused by endogenous expression of mutant huntingtin in a striatal cell line from the HdhQ111/Q111 knock-in mouse. Results We screened the NINDS Custom Collection of 1,040 FDA approved drugs and bioactive compounds for their ability to prevent in vitro aggregation of Q58-htn 1–171 amino terminal fragment. Ten compounds were identified that inhibited aggregation with IC50 < 15 μM, including gossypol, gambogic acid, juglone, celastrol, sanguinarine and anthralin. Of these, both juglone and celastrol were effective in reversing the abnormal cellular localization of full-length mutant huntingtin observed in mutant HdhQ111/Q111 striatal cells. Conclusions At least some compounds identified as aggregation inhibitors also prevent a neuronal cellular phenotype caused by full-length mutant huntingtin, suggesting that in vitro fragment aggregation can act as a proxy for monitoring the disease-producing conformational property in HD. Thus, identification and testing of compounds that alter in vitro aggregation is a viable approach for defining potential therapeutic compounds that may act on the deleterious conformational property of full-length mutant huntingtin. PMID:15649316

The characterization of a zebrafish mid-hindbrain mutant, mid-hindbrain gone (mgo).

PubMed

Shima, Takaki; Znosko, Wade; Tsang, Michael

2009-04-01

The vertebrate mid-hindbrain boundary (MHB) is a crucial morphological structure required for patterning and neural differentiation of the midbrain and anterior hindbrain. We isolated a novel zebrafish mutant, MHB gone (mgo), that exhibited a defective MHB. Expression of engrailed3 in the prospective MHB was absent at the 1-somite stage, suggesting that initiation of the isthmic organizer was disrupted in mgo mutants. Complementation test with mgo and noi, in which the pax2a gene is mutated, infer that the mgo mutant may represent a novel noi allele. However, pronephric, otic vesicle, and commissural axonal defects described in noi mutants were not associated with mgo mutants. Genetic mapping revealed that the mgo mutation is linked to the Pax2a locus, but no mutation was detected in pax2a exons or within intron-exon boundaries. Based on these findings, we propose that the mgo mutation genetically interacts with pax2a required for the initiation of MHB formation. Copyright 2009 Wiley-Liss, Inc.

Mutant SOD1 in cell types other than motor neurons and oligodendrocytes accelerates onset of disease in ALS mice

PubMed Central

Yamanaka, Koji; Boillee, Severine; Roberts, Elizabeth A.; Garcia, Michael L.; McAlonis-Downes, Melissa; Mikse, Oliver R.; Cleveland, Don W.; Goldstein, Lawrence S. B.

2008-01-01

Dominant mutations in ubiquitously expressed superoxide dismutase (SOD1) cause familial ALS by provoking premature death of adult motor neurons. To test whether mutant damage to cell types beyond motor neurons is required for the onset of motor neuron disease, we generated chimeric mice in which all motor neurons and oligodendrocytes expressed mutant SOD1 at a level sufficient to cause fatal, early-onset motor neuron disease when expressed ubiquitously, but did so in a cellular environment containing variable numbers of non-mutant, non-motor neurons. Despite high-level mutant expression within 100% of motor neurons and oligodendrocytes, in most of these chimeras, the presence of WT non-motor neurons substantially delayed onset of motor neuron degeneration, increasing disease-free life by 50%. Disease onset is therefore non-cell autonomous, and mutant SOD1 damage within cell types other than motor neurons and oligodendrocytes is a central contributor to initiation of motor neuron degeneration. PMID:18492803

Simulation turbulenter Konvektion in Supernova-Explosionen massereicher Sterne.

NASA Astrophysics Data System (ADS)

Janka, H.-T.; Müller, E.; Ruffert, M.

Contents: 1. Das Projekt: Numerische Simulation von Typ-II-Supernovae. 2. Die numerischen Verfahren. 3. Die Visualisierung von dreidimensionalen Datensätzen. 4. Die Ergebnisse: Einblick in explodierende Sterne.

Wernher von Braun

NASA Image and Video Library

1967-08-28

Marshall Space Flight Center’s (MSFC) director, Dr. Wernher von Braun (right), inspects a component of a laser experiment being conducted in MSFC’s Space Sciences Laboratory during a tour on August 28, 1967.

Blood Disorders

MedlinePlus

... become hard, sticky, and shaped like a C. Thalassemia Red blood cell disorder. Von Willebrand Disease Blood ... Hemophilia Hereditary Hemorrhagic Telangiectasia (HHT) Sickle Cell Disease Thalassemia Vitamin K Deficiency Bleeding Von Willebrand Disease Women’s ...

Wernher von Braun

NASA Image and Video Library

1962-09-11

Marshall Space Flight Center Director Dr. Wernher von Braun explains a detail from a Saturn IB mockup and engine to President John F. Kennedy, Vice President Lyndon Johnson and other guests, September 11, 1962.

Determining the von Mises stress power spectral density for frequency domain fatigue analysis including out-of-phase stress components

NASA Astrophysics Data System (ADS)

Bonte, M. H. A.; de Boer, A.; Liebregts, R.

2007-04-01

This paper provides a new formula to take into account phase differences in the determination of an equivalent von Mises stress power spectral density (PSD) from multiple random inputs. The obtained von Mises PSD can subsequently be used for fatigue analysis. The formula was derived for use in the commercial vehicle business and was implemented in combination with Finite Element software to predict and analyse fatigue failure in the frequency domain.

Himmelsfotografie MIT Schmidt-Teleskopen

NASA Astrophysics Data System (ADS)

Marx, Siegfried; Pfau, Werner

Auf dem Höhepunkt der Verbreitung und astronomischen Anwendung von Schmidt-Teleskopen legen S. Marx und W. Pfau einen reich illustrierten Bildband zu diesem Fernrohrtyp vor. Der thematische Bogen reicht von der Teleskoptechnik und ihrer Geschichte über das Leben von Berhard Schmidt bis zu den schönsten, hier in hervorragender Qualität wiedergegebenen Himmelsaufnahmen und ihrer wissenschaftlichen Interpretation. Praktische Hinweise zu eigener fotografischer Tätigkeit und ein Glossar machen das Buch nützlich für jeden Liebhaber der Himmelskunde.

Western Foreign Fighters in Syria: An Empirical Analysis of Recruitment and Mobilization Mechanisms

DTIC Science & Technology

2015-06-01

Malet, Foreign Fighters, 5. 16 Ibid., 4–6. 17 See for example Ines von Behr, Anaïs Reding , Charlie Edwards, and Luke Gribbon, “Radicalization in the...summary see Ines von Behr, Anaïs Reding , Charlie Edwards, and Luke Gribbon, “Radicalization in the Digital Era: The Use of the Internet in 15 Cases of...12; <http://www.lexisnexis.com.libproxy.nps.edu/hottopics/lnacademic> [April 11, 2015]. 134 von Behr, Reding , Edwards, and Gribbon

Image Understanding Workshop. Proceedings of a Workshop Held in Los Angeles, California on 23-25 February 1987. Volume 2

DTIC Science & Technology

1987-02-25

Modellierung von Kanten bei unregel. Navigation within a building, to be published in IEEE mifliger Rasterung in Bildverarbeitun uand Muster...converted them into equivalent machine cycles in Table 3-1. We took into account of 100 nanosecond 0 - 0, machine cycle time of the MPP. In MPP, NON- VON ...We show the result for the conjugate gradient method in of NON- VON . We assumed that the instructions which carry Table 4-4. The computation of four

Von Donuts und Zucker: Mit Neutronen biologische Makromoleküle erforschen

NASA Astrophysics Data System (ADS)

May, Roland P.

2003-05-01

Für die Erforschung von Biomolekülen bieten Neutronen einzigartige Eigenschaften. Vor allem ihre unterschiedliche Wechselwirkung mit dem natürlichen Wasserstoff und seinem schweren Isotop Deuterium ermöglicht tiefe Einblicke in Struktur, Funktion und Dynamik von Proteinen, Nukleinsäuren und Biomembranen. Bei vielen Fragestellungen zur Strukturaufklärung gibt es kaum oder keine Alternative zum Neutron. Das Institut Laue-Langevin trägt Bahnbrechendes zum Erfolg der Neutronen-Methoden in der Biologie bei.

Letters by Franz Xaver von Zach to Ranieri Gerbi and Pompilio Pozzetti. (German Title: Briefe von Franz Xaver von Zach an Ranieri Gerbi und Pompilio Pozzetti)

NASA Astrophysics Data System (ADS)

Meschiari, Alberto

Two letters by Zach to the physicist Gerbi at Pisa and one to the librarian Pozzetti at Bologna confirm once more the role of the first as collector and distributor of scientific information. In the second letter to Gerbi, Zach ensures the recipient that he had rightfully criticized the optical contributions of Goethe and that the latter doesn't enjoy any reputation as a scientist.

Beschallungstechnik, Beschallungsplanung und Simulation

NASA Astrophysics Data System (ADS)

Ahnert, Wolfgang; Goertz, Anselm

Die primäre Aufgabe einer Lautsprecheranlage ist es, Musik, Sprache oder auch Signaltöne und Geräusche wiederzugeben. Diese können von einem Tonträger kommen (CD, Sprachspeicher), von einem anderen Ort übertragen (Zuspielung über Radio, TV, Telefon) oder vor Ort erzeugt werden. Letzteres umfasst Konzerte, Ansprachen, Durchsagen oder künstlerische Darbietungen, bei denen es meist darum geht, eine bereits vorhandene Quelle einer größeren oder weiter verteilten Anzahl von Personen zugänglich zu machen.

Dr. von Braun With Management Team

NASA Technical Reports Server (NTRS)

1961-01-01

Dr. von Braun is shown in this photograph, which was probably taken in the early 1960s, with members of his management team. Pictured from left to right are, Werner Kuers, Director of the Manufacturing Engineering Division; Dr. Walter Haeussermarn, Director of the Astrionics Division; Dr. William Mrazek, Propulsion and Vehicle Engineering Division; Dr. von Braun; Dieter Grau, Director of the Quality Assurance Division; Dr. Oswald Lange, Director of the Saturn Systems Office; and Erich Neubert , Associate Deputy Director for Research and Development.

Nazi Germany and Fascist Italy: Totalitarian Menace or Monolithic Illusion? An Analysis of the Axis Coalition

DTIC Science & Technology

2004-06-17

no confidence in against Chancellor Franz von Papen . This led to new elections on 6 November which had unintended consequences--the Nazi’s lost 2...their living space and to maintain peace.1 Preamble to the Pact of Steel On 22 May 1939, the German Reich Minister for Foreign Affairs, Joachim von ...alliance and war. 5 In Germany, Hitler continued to accumulate power after January 1933. With the death of President Paul von Hindenburg, Hitler

Establishing Post-Conflict Justice Through U.S. Occupation: Military Tribunals as a Means of Transitional Justice

DTIC Science & Technology

2013-03-01

the former chancellor Franz von Papen , who stayed on as Hitler’s vice-chancellor for the early years of the Third Reich; and Economics Minister... Papen , Franz von I I - - Acquitted Chancellor of Germany 1932, Vice-Chancellor under Hilter 1933-1934 Raeder, Erich G G G - Life in Prison...and Foreign Minister Joachim von Ribbentrop.22 (The Soviet judge was on record at the time, griping that too few of the defendants were sentenced to

Comparison of the U.S. and German Approaches to Democratic Civil-Military Relations

DTIC Science & Technology

2003-06-01

the former General, Franz von Papen , who was the war-time military attaché in the United States, Craig, p. 455. 307 Craig, p. 454. 68 army to bear...against the Chancellor von Papen and became Chancellor himself in December 1932. Another attempt to convince the Nazis to take part as junior...Finally, high ranking officers of the Reichswehr, like Schleicher and von Papen , were deeply involved in politics, which led to the rise of

Wernher von Braun

NASA Image and Video Library

1970-06-27

This photograph was taken after Dr. von Braun moved from his post as Director of the Marshall Space Flight Center (MSFC) to Deputy Associate Administrator for Planning at NASA Headquarters. On June 27, 1970, he visited the MSFC again during the center’s 10th anniversary to look at a mockup of the spacecraft that would later be known as Skylab. With von Braun are (left to right): Herman K. Weidner, director of Science and Engineering at MSFC, and James R. Thompson of the center’s Astrionics Laboratory.

In vitro susceptibility of four antimicrobials against Riemerella anatipestifer isolates: a comparison of minimum inhibitory concentrations and mutant prevention concentrations for ceftiofur, cefquinome, florfenicol, and tilmicosin.

PubMed

Li, Yafei; Zhang, Yanan; Ding, Huanzhong; Mei, Xian; Liu, Wei; Zeng, Jiaxiong; Zeng, Zhenling

2016-11-09

Mutant prevention concentration (MPC) is an alternative pharmacodynamic parameter that has been used to measure antimicrobial activity and represents the propensities of antimicrobial agents to select resistant mutants. The concentration range between minimum inhibitory concentration (MIC) and MPC is defined as mutant selection window (MSW). The MPC and MSW parameters represent the ability of antimicrobial agents to inhibit the bacterial mutants selected. This study was conducted to determine the MIC and MPC values of four antimicrobials including ceftiofur, cefquinome, florfenicol and tilmicosin against 105 Riemerella anatipestifer isolates. The MIC 50 /MIC 90 values of clinical isolates tested in our study for ceftiofur, cefquinome, florfenicol and tilmicosin were 0.063/0.5、0.031/0.5、1/4、1/4 μg/mL, respectively; MPC 50 / MPC 90 values were 4/64、8/64、4/32、16/256 μg/mL, respectively. These results provided information on the use of these compounds in treating the R. anatipestifer infection; however, additional studies are needed to demonstrate their therapeutic efficacy. Based on the MSW theory, the hierarchy of these tested antimicrobial agents with respect to selecting resistant subpopulations was as follows: cefquinome > ceftiofur > tilmicosin > florfenicol. Cefquinome was the drug that presented the highest risk of selecting resistant mutant among the four antimicrobial agents.

Regulated Exopolysaccharide Production in Myxococcus xanthus

PubMed Central

Kim, Sang-Hoon; Ramaswamy, Srinivas; Downard, John

1999-01-01

Myxococcus xanthus fibrils are cell surface-associated structures composed of roughly equal amounts of polysaccharide and protein. The level of M. xanthus polysaccharide production under different conditions in the wild type and in several mutants known to have alterations in fibril production was investigated. Wild-type exopolysaccharide increased significantly as cells entered the stationary phase of growth or upon addition of Ca2+ to growing cells, and the polysaccharide-induced cells exhibited an enhanced capacity for cell-cell agglutination. The activity of the key gluconeogenic pathway enzyme phosphoenolpyruvate carboxykinase (Pck) also increased under these conditions. Most fibril-deficient mutants failed to produce polysaccharide in a stationary-phase- or Ca2+-dependent fashion. However, regulation of Pck activity was generally unimpaired in these mutant strains. In an stk mutant, which overproduces fibrils, polysaccharide production and Pck activity were constitutively high under the conditions tested. Polysaccharide production increased in most fibril-deficient strains when an stk mutant allele was present, indicating that these fibril-deficient mutants retained the basic cellular components required for fibril polysaccharide production. In contrast to other divalent cations tested, Sr2+ effectively replaced Ca2+ in stimulating polysaccharide production, and either Ca2+ or Sr2+ was required for fruiting-body formation by wild-type cells. By using transmission electron microscopy of freeze-substituted log-phase wild-type cells, fibril material was observed as a cell surface-associated layer of uniform thickness composed of filaments with an ordered structure. PMID:10049381

Exercise induced von Willebrand Factor release -- new model for routine endothelial testing.

PubMed

Balen, Sanja; Ruzić, Alen; Mirat, Jure; Persić, Viktor

2007-01-01

Endothelial dysfunction (ED) is actively involved in the mechanism of occurrence, development and progression of all the degrees of atherosclerosis. The established impact of ED on the progress and outcome of cardiovascular diseases, together with convincing indications of a possible successful therapeutic modification, necessitate the changeover of ED assessment from experimental to a routine practice. As there is no appropriate method for a clinical practice, scientists anticipate significant research efforts in the further development. Among numerous methods already available, von Willebrand Factor (vWF) stands out significantly. In accordance with the accepted leading diagnostic role of vWF baseline levels in the group of peripheral endothelial markers, and earlier scientific observations on the absence of its expected reactivation during physical exercise, we hypothesised this promising theory. We believe that a constant stronger release of vWF in endothelial cell injury leads to the exhaustion of its stores in Weibel-Palade bodies with the consequent absence of the expected rise of concentration during the exercise. Therefore, we hypothesised that ED could be exhaustible vWF endothelopathy and the exercise induced release of vWF a new, simple, safe and reliable test for the detection of ED and monitoring of the expected therapeutic effect. In order to have a final clinical usability of the proposed diagnostic model, it is necessary to test its reliability in different pathological and risk states, and establish susceptibility in therapeutic procedures. The correlation with invasive functional angiographic tests and the flow mediated dilatation test of peripheral arteries also needs to be validated. We expect the proposed test of vWF inducibility to find its place in clinical practice, i.e. in prevention, prediction and therapy of cardiovascular diseases.

Development and characterization of mutant winter wheat (Triticum aestivum L.) accessions resistant to the herbicide quizalofop.

PubMed

Ostlie, Michael; Haley, Scott D; Anderson, Victoria; Shaner, Dale; Manmathan, Harish; Beil, Craig; Westra, Phillip

2015-02-01

New herbicide resistance traits in wheat were produced through the use of induced mutagenesis. While herbicide-resistant crops have become common in many agricultural systems, wheat has seen few introductions of herbicide resistance traits. A population of Hatcher winter wheat treated with ethyl methanesulfonate was screened with quizalofop to identify herbicide-resistant plants. Initial testing identified plants that survived multiple quizalofop applications. A series of experiments were designed to characterize this trait. In greenhouse studies the mutants exhibited high levels of quizalofop resistance compared to non-mutant wheat. Sequencing ACC1 revealed a novel missense mutation causing an alanine to valine change at position 2004 (Alopecurus myosuroides reference sequence). Plants carrying single mutations in wheat's three genomes (A, B, D) were identified. Acetyl co-enzyme A carboxylase in resistant plants was 4- to 10-fold more tolerant to quizalofop. Populations of segregating backcross progenies were developed by crossing each of the three individual mutants with wild-type wheat. Experiments conducted with these populations confirmed largely normal segregation, with each mutant allele conferring an additive level of resistance. Further tests showed that the A genome mutation conferred the greatest resistance and the B genome mutation conferred the least resistance to quizalofop. The non-transgenic herbicide resistance trait identified will enhance weed control strategies in wheat.

Leaf hydraulic conductance varies with vein anatomy across Arabidopsis thaliana wild-type and leaf vein mutants.

PubMed

Caringella, Marissa A; Bongers, Franca J; Sack, Lawren

2015-12-01

Leaf venation is diverse across plant species and has practical applications from paleobotany to modern agriculture. However, the impact of vein traits on plant performance has not yet been tested in a model system such as Arabidopsis thaliana. Previous studies analysed cotyledons of A. thaliana vein mutants and identified visible differences in their vein systems from the wild type (WT). We measured leaf hydraulic conductance (Kleaf ), vein traits, and xylem and mesophyll anatomy for A. thaliana WT (Col-0) and four vein mutants (dot3-111 and dot3-134, and cvp1-3 and cvp2-1). Mutant true leaves did not possess the qualitative venation anomalies previously shown in the cotyledons, but varied quantitatively in vein traits and leaf anatomy across genotypes. The WT had significantly higher mean Kleaf . Across all genotypes, there was a strong correlation of Kleaf with traits related to hydraulic conductance across the bundle sheath, as influenced by the number and radial diameter of bundle sheath cells and vein length per area. These findings support the hypothesis that vein traits influence Kleaf , indicating the usefulness of this mutant system for testing theory that was primarily established comparatively across species, and supports a strong role for the bundle sheath in influencing Kleaf . © 2015 John Wiley & Sons Ltd.

Jasmonate is essential for insect defense in Arabidopsis.

PubMed

McConn, M; Creelman, R A; Bell, E; Mullet, J E; Browse, J

1997-05-13

The signaling pathways that allow plants to mount defenses against chewing insects are known to be complex. To investigate the role of jasmonate in wound signaling in Arabidopsis and to test whether parallel or redundant pathways exist for insect defense, we have studied a mutant (fad3-2 fad7-2 fad8) that is deficient in the jasmonate precursor linolenic acid. Mutant plants contained negligible levels of jasmonate and showed extremely high mortality ( approximately 80%) from attack by larvae of a common saprophagous fungal gnat, Bradysia impatiens (Diptera: Sciaridae), even though neighboring wild-type plants were largely unaffected. Application of exogenous methyl jasmonate substantially protected the mutant plants and reduced mortality to approximately 12%. These experiments precisely define the role of jasmonate as being essential for the induction of biologically effective defense in this plant-insect interaction. The transcripts of three wound-responsive genes were shown not to be induced by wounding of mutant plants but the same transcripts could be induced by application of methyl jasmonate. By contrast, measurements of transcript levels for a gene encoding glutathione S-transferase demonstrated that wound induction of this gene is independent of jasmonate synthesis. These results indicate that the mutant will be a good genetic model for testing the practical effectiveness of candidate defense genes.

Jasmonate is essential for insect defense in Arabidopsis

PubMed Central

McConn, Michele; Creelman, Robert A.; Bell, Erin; Mullet, John E.; Browse, John

1997-01-01

The signaling pathways that allow plants to mount defenses against chewing insects are known to be complex. To investigate the role of jasmonate in wound signaling in Arabidopsis and to test whether parallel or redundant pathways exist for insect defense, we have studied a mutant (fad3–2 fad7–2 fad8) that is deficient in the jasmonate precursor linolenic acid. Mutant plants contained negligible levels of jasmonate and showed extremely high mortality (≈80%) from attack by larvae of a common saprophagous fungal gnat, Bradysia impatiens (Diptera: Sciaridae), even though neighboring wild-type plants were largely unaffected. Application of exogenous methyl jasmonate substantially protected the mutant plants and reduced mortality to ≈12%. These experiments precisely define the role of jasmonate as being essential for the induction of biologically effective defense in this plant–insect interaction. The transcripts of three wound-responsive genes were shown not to be induced by wounding of mutant plants but the same transcripts could be induced by application of methyl jasmonate. By contrast, measurements of transcript levels for a gene encoding glutathione S-transferase demonstrated that wound induction of this gene is independent of jasmonate synthesis. These results indicate that the mutant will be a good genetic model for testing the practical effectiveness of candidate defense genes. PMID:11038546

Wernher von Braun

NASA Image and Video Library

1962-01-01

Dr. Wernher von Braun, Director of the Marshall Space Flight Center (MSFC), during his tour of the Space information Division of North American Aviation (NAA) in Downey, California, where the Saturn SII stage was developed.

Wernher von Braun

NASA Image and Video Library

1964-10-14

This photograph, dated October 14, 1964, was taken at the Marned Spacecraft Center, now the Johnson Space Center in Houston, Texas. Dr. von Braun is shown looking over consoles in the Manned Spaceflight Control Center.

Corrector VX-809 stabilizes the first transmembrane domain of CFTR.

PubMed

Loo, Tip W; Bartlett, M Claire; Clarke, David M

2013-09-01

Processing mutations that inhibit folding and trafficking of CFTR are the main cause of cystic fibrosis (CF). A potential CF therapy would be to repair CFTR processing mutants. It has been demonstrated that processing mutants of P-glycoprotein (P-gp), CFTR's sister protein, can be efficiently repaired by a drug-rescue mechanism. Many arginine suppressors that mimic drug-rescue have been identified in the P-gp transmembrane (TM) domains (TMDs) that rescue by forming hydrogen bonds with residues in adjacent helices to promote packing of the TM segments. To test if CFTR mutants could be repaired by a drug-rescue mechanism, we used truncation mutants to test if corrector VX-809 interacted with the TMDs. VX-809 was selected for study because it is specific for CFTR, it is the most effective corrector identified to date, but it has limited clinical benefit. Identification of the VX-809 target domain will help to develop correctors with improved clinical benefits. It was found that VX-809 rescued truncation mutants lacking the NBD2 and R domains. When the remaining domains (TMD1, NBD1, TMD2) were expressed as separate polypeptides, VX-809 only increased the stability of TMD1. We then performed arginine mutagenesis on TM6 in TMD1. Although the results showed that TM6 had distinct lipid and aqueous faces, CFTR was different from P-gp as no arginine promoted maturation of CFTR processing mutants. The results suggest that TMD1 contains a VX-809 binding site, but its mechanism differed from P-gp drug-rescue. We also report that V510D acts as a universal suppressor to rescue CFTR processing mutants. Copyright © 2013 Elsevier Inc. All rights reserved.

The extradomain a of fibronectin enhances the efficacy of lipopolysaccharide defective Salmonella bacterins as vaccines in mice

PubMed Central

2012-01-01

The Extradomain A from fibronectin (EDA) has an immunomodulatory role as fusion protein with viral and tumor antigens, but its effect when administered with bacteria has not been assessed. Here, we investigated the adjuvant effect of EDA in mice immunizations against Salmonella enterica subspecies enterica serovar Enteritidis (Salmonella Enteritidis). Since lipopolysaccharide (LPS) is a major virulence factor and the LPS O-polysaccharide (O-PS) is the immunodominant antigen in serological diagnostic tests, Salmonella mutants lacking O-PS (rough mutants) represent an interesting approach for developing new vaccines and diagnostic tests to differentiate infected and vaccinated animals (DIVA tests). Here, antigenic preparations (hot-saline extracts and formalin-inactivated bacterins) from two Salmonella Enteritidis rough mutants, carrying either intact (SEΔwaaL) or deep-defective (SEΔgal) LPS-Core, were used in combination with EDA. Biotinylated bacterins, in particular SEΔwaaL bacterin, decorated with EDAvidin (EDA and streptavidin fusion protein) improved the protection conferred by hot-saline or bacterins alone and prevented significantly the virulent infection at least to the levels of live attenuated rough mutants. These findings demonstrate the adjuvant effect of EDAvidin when administered with biotinylated bacterins from Salmonella Enteritidis lacking O-PS and the usefulness of BEDA-SEΔwaaL as non-live vaccine in the mouse model. PMID:22515195

Computation, prediction, and experimental tests of fitness for bacteriophage T7 mutants with permuted genomes

NASA Astrophysics Data System (ADS)

Endy, Drew; You, Lingchong; Yin, John; Molineux, Ian J.

2000-05-01

We created a simulation based on experimental data from bacteriophage T7 that computes the developmental cycle of the wild-type phage and also of mutants that have an altered genome order. We used the simulation to compute the fitness of more than 105 mutants. We tested these computations by constructing and experimentally characterizing T7 mutants in which we repositioned gene 1, coding for T7 RNA polymerase. Computed protein synthesis rates for ectopic gene 1 strains were in moderate agreement with observed rates. Computed phage-doubling rates were close to observations for two of four strains, but significantly overestimated those of the other two. Computations indicate that the genome organization of wild-type T7 is nearly optimal for growth: only 2.8% of random genome permutations were computed to grow faster, the highest 31% faster, than wild type. Specific discrepancies between computations and observations suggest that a better understanding of the translation efficiency of individual mRNAs and the functions of qualitatively "nonessential" genes will be needed to improve the T7 simulation. In silico representations of biological systems can serve to assess and advance our understanding of the underlying biology. Iteration between computation, prediction, and observation should increase the rate at which biological hypotheses are formulated and tested.

Wernher von Braun

NASA Image and Video Library

1959-03-03

Dr. von Braun, Director of the Development Operations Divisons, and Dr. Debus, Director of the Missile Firing Laboratory; Army Ballistic Missile Agency (ABMA), in the blockhouse during the launch of the Pioneer IV, March 3, 1959.

A Novel Approach for Effectively Treating SCI Pain, Improving Opioid Efficacy, and Preventing Opioid-Induced Constipation: Key Role of Toll-Like Receptor 4 (TLR4)

DTIC Science & Technology

2014-10-01

RESPONSIBLE PERSON USAMRMC a. REPORT U b. ABSTRACT U c. THIS PAGE U UU 17 19b. TELEPHONE NUMBER (include area code ) 2 Table of Contents...after dorsal root avulsion, during the acute stages of injury? 3b. SNAP surgery and testing (Hargreaves, motor function and constipation tests during the...first week post- surgery with co-administration of morphine and (+)-naltrexone (vs. vehicles) starting 1 or 24 hr post surgery ; von Frey and motor

Mutation Testing for Effective Verification of Digital Components of Physical Systems

NASA Astrophysics Data System (ADS)

Kushik, N. G.; Evtushenko, N. V.; Torgaev, S. N.

2015-12-01

Digital components of modern physical systems are often designed applying circuitry solutions based on the field programmable gate array technology (FPGA). Such (embedded) digital components should be carefully tested. In this paper, an approach for the verification of digital physical system components based on mutation testing is proposed. The reference description of the behavior of a digital component in the hardware description language (HDL) is mutated by introducing into it the most probable errors and, unlike mutants in high-level programming languages, the corresponding test case is effectively derived based on a comparison of special scalable representations of the specification and the constructed mutant using various logic synthesis and verification systems.

Towards a "Golden Standard" for computing globin stability: Stability and structure sensitivity of myoglobin mutants.

PubMed

Kepp, Kasper P

2015-10-01

Fast and accurate computation of protein stability is increasingly important for e.g. protein engineering and protein misfolding diseases, but no consensus methods exist for important proteins such as globins, and performance may depend on the type of structural input given. This paper reports benchmarking of six protein stability calculators (POPMUSIC 2.1, I-Mutant 2.0, I-Mutant 3.0, CUPSAT, SDM, and mCSM) against 134 experimental stability changes for mutations of sperm-whale myoglobin. Six different high-resolution structures were used to test structure sensitivity that may impair protein calculations. The trend accuracy of the methods decreased as I-Mutant 2.0 (R=0.64-0.65), SDM (R=0.57-0.60), POPMUSIC2.1 (R=0.54-0.57), I-Mutant 3.0 (R=0.53-0.55), mCSM (R=0.35-0.47), and CUPSAT (R=0.25-0.48). The mean signed errors increased as SDM

Characterization of multilocus lesions in human cells exposed to X radiation and radon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chaudhry, M.A.; Jiang, Q.; Ricanati, M.

Human TK6 lymphoblasts were exposed to X radiation or radon, and thymidine kinase negative (TK{sup -/-}) mutants were selected, isolated and harvested for analysis of structural changes in the TK gene. A large majority (82%) of the radon-induced mutants, 74% of the X-radiation-induced mutants and 45% of the spontaneous mutants lost the entire active TK allele. To analyze these mutants further we measured the loss of heterozygosity at several loci neighboring the TK locus on chromosome 17q. A greater proportion (61%) of the radon-induced mutants than X-radiation-induced or spontaneous mutants harbored the smaller lesions involving the TK allele alone ormore » extending from the TK locus to one or both of the closest neighboring sequences tested. Further, 21% of the X-radiation-induced mutants but only 5% of the radon-induced mutants lost heterozygosity at the col1A1 locus, 31 Mb from the TK gene. These results are in agreement with a recent analysis of radon- and X-radiation-induced lesions inactivating the HPRT gene of TK6 cells, in which we reported that a lower percentage of radon- than X-radiation-induced mutants showed lesions extending to markers 800 kb or more from the HPRT gene on the X chromosome. In the present study, we observed that the percentage of slowly growing and very slowly growing TK{sup -/-} mutants was greater after treatment with radon than after treatment with X radiation, regardless of the type of lesion present. It is possible, therefore, that the radon-induced lesions are complex and/or less easily repaired, leading to slow growth in a large proportion of the surviving mutant cells. 36 refs., 6 figs., 2 tabs.« less

Dual MAPK inhibition is an effective therapeutic strategy for a subset of class II BRAF mutant melanoma.

PubMed

Dankner, Matthew; Lajoie, Mathieu; Moldoveanu, Dan; Nguyen, Tan-Trieu; Savage, Paul; Rajkumar, Shivshankari; Huang, Xiu; Lvova, Maria; Protopopov, Alexei; Vuzman, Dana; Hogg, David; Park, Morag; Guiot, Marie-Christine; Petrecca, Kevin; Mihalcioiu, Catalin; Watson, Ian R; Siegel, Peter M; Rose, April A N

2018-06-14

Dual MAPK pathway inhibition (dMAPKi) with BRAF and MEK inhibitors improves survival in BRAF V600E/K mutant melanoma, but the efficacy of dMAPKi in non-V600 BRAF mutant tumors is poorly understood. We sought to characterize the responsiveness of class II (enhanced kinase activity, dimerization dependent) BRAF mutant melanoma to dMAPKi. Tumors from patients with BRAF WT, V600E (class I) and L597S (class II) metastatic melanoma were used to generate patient-derived-xenografts (PDX). We assembled a panel of melanoma cell lines with class IIa (activation segment) or IIb (p-loop) mutations and compared these to wild-type or V600E/K BRAF mutant cells. Cell lines and PDXs were treated with BRAFi (vemurafenib, dabrafenib, encorafenib, LY3009120), MEKi (cobimetinib, trametinib, binimetinib) or the combination. We identified two patients with BRAF L597S metastatic melanoma who were treated with dMAPKi. BRAFi impaired MAPK signalling and cell growth in class I and II BRAF mutant cells. dMAPKi was more effective than either single MAPKi at inhibiting cell growth in all class II BRAF mutant cells tested. dMAPKi caused tumor regression in two melanoma PDXs with class II BRAF mutations, and prolonged survival of mice with class II BRAF mutant melanoma brain metastases. Two patients with BRAF L597S mutant melanoma clinically responded to dMAPKi. Class II BRAF mutant melanoma are growth inhibited by dMAPKi. Responses to dMAPKi have been observed in two patients with class II BRAF mutant melanoma. This data provides rationale for clinical investigation of dMAPKi in patients with class II BRAF mutant metastatic melanoma. Copyright ©2018, American Association for Cancer Research.

Evidence that tRNA modifying enzymes are important in vivo targets for 5-fluorouracil in yeast

PubMed Central

Gustavsson, Marie; Ronne, Hans

2008-01-01

We have screened a collection of haploid yeast knockout strains for increased sensitivity to 5-fluorouracil (5-FU). A total of 138 5-FU sensitive strains were found. Mutants affecting rRNA and tRNA maturation were particularly sensitive to 5-FU, with the tRNA methylation mutant trm10 being the most sensitive mutant. This is intriguing since trm10, like many other tRNA modification mutants, lacks a phenotype under normal conditions. However, double mutants for nonessential tRNA modification enzymes are frequently temperature sensitive, due to destabilization of hypomodified tRNAs. We therefore tested if the sensitivity of our mutants to 5-FU is affected by the temperature. We found that the cytotoxic effect of 5-FU is strongly enhanced at 38°C for tRNA modification mutants. Furthermore, tRNA modification mutants show similar synthetic interactions for temperature sensitivity and sensitivity to 5-FU. A model is proposed for how 5-FU kills these mutants by reducing the number of tRNA modifications, thus destabilizing tRNA. Finally, we found that also wild-type cells are temperature sensitive at higher concentrations of 5-FU. This suggests that tRNA destabilization contributes to 5-FU cytotoxicity in wild-type cells and provides a possible explanation why hyperthermia can enhance the effect of 5-FU in cancer therapy. PMID:18314501

Phenotypic characterization of adenovirus type 12 temperature-sensitive mutants in productive infection and transformation.

PubMed

Hama, S; Kimura, G

1980-01-01

Eleven temperature-sensitive mutants of adenovirus type 12, capable of forming plaques in human cells at 33 C but not at 39.5 C, were isolated from a stock of a wild-type strain after treatment with either nitrous acid or hydroxylamine. Complementation tests in doubly infected human cells permitted a tentative assignment of eight of these mutants to six complementation groups. Temperature-shift experiments revealed that one mutant is affected early and most of the other mutants are affected late. Only the early mutant, H12ts505, was temperature sensitive in viral DNA replication. Infectious virions of all the mutants except H12ts505 and two of the late mutants produced at 33 C, appeared to be more heat labile than those of the wild type. Only H12ts505 was temperature sensitive for the establishment of transformation of rat 3Y1 cells. One of the late mutants (H12ts504) had an increased transforming ability at the permissive temperature. Results of temperature-shift transformation experiments suggest that a viral function affected in H12ts505 is required for "initiation" of transformation. Some of the growth properties of H12ts505-transformed cells were also temperature dependent, suggesting that a functional expression of a gene mutation in H12ts505 is required to maintain at least some aspects of the transformed state.

Genetic studies of cell fusion induced by herpes simplex virus type 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Read, G.S.; Person, S.; Keller, P.M.

1980-07-01

Eight cell fusion-causing syn mutants were isolated from the KOS strain of herpes simplex virus type 1. Unlike the wild-type virus, the mutants produced plaques containing multinucleated cells, or syncytia. Fusion kinetics curves were established with a Coulter Counter assay for the mutants and wild-type virus in single infections of human embryonic lung (HEL) cells, for the mutants and wild-type virus in mixed infections (dominance test), and for pairs of mutants in mixed infection and proceeded with an exponential decrease in the number of small single cells. At some later time that was characteristic of the mutant, there was amore » significant reduction in the rate of fusion for all but possibly one of the mutants. Although the wild-type virus did not produce syncytial plaques, it did induce a small amount of fusion that stopped abruptly about 2 h after it started. These data are consistent with the hypothesis that both mutants and wild type induce an active fusion inducer and that the activity of this inducer is subsequently inhibited. The extent of fusion is apparently determined by the length of the interval during which the fusion inducer is active. That fusion is actively inhibited in wild-type infections is indicated by the observation that syn mutant-infected cells fused more readily with uninfected cells than with wild type-infected cells.« less

The mitochondrial cytochrome c peroxidase Ccp1 of Saccharomyces cerevisiae is involved in conveying an oxidative stress signal to the transcription factor Pos9 (Skn7).

PubMed

Charizanis, C; Juhnke, H; Krems, B; Entian, K D

1999-10-01

In Saccharomyces cerevisiae two transcription factors, Pos9 (Skn7) and Yap1, are involved in the response to oxidative stress. Fusion of the Pos9 response-regulator domain to the Gal4 DNA-binding domain results in a transcription factor which renders the expression of a GAL1-lacZ reporter gene dependent on oxidative stress. To identify genes which are involved in the oxygen-dependent activation of the Gal4-Pos9 hybrid protein we screened for mutants that failed to induce the heterologous test system upon oxidative stress (fap mutants for factors activating Pos9). We isolated several respiration-deficient and some respiration-competent mutants by this means. We selected for further characterization only those mutants which also displayed an oxidative-stress-sensitive phenotype. One of the respiration-deficient mutants (complementation groupfap6) could be complemented by the ISM1 gene, which encodes mitochondrial isoleucyl tRNA synthetase, suggesting that respiration competence was important for signalling of oxidative stress. In accordance with this notion a rho0 strain and a wild-type strain in which respiration had been blocked (by treatment with antimycin A or with cyanide) also failed to activate Gal4-Pos9 upon imposition of oxidative stress. Another mutant, fap24, which was respiration-competent, could be complemented by CCP1, which encodes the mitochondrial cytochrome c peroxidase. Mitochondrial cytochrome c peroxidase degrades reactive oxygen species within the mitochondria. This suggested a possible sensor function for the enzyme in the oxidative stress response. To test this we used the previously described point mutant ccp1 W191F, which is characterized by a 10(4)-fold decrease in electron flux between cytochrome c and cytochrome c peroxidase. The Ccp1W191F mutant was still capable of activating the Pos9 transcriptional activation domain, suggesting that the signalling function of Ccp1 is independent of electron flux rates.

Determining the Advantages, Costs, and Trade-Offs of a Novel Sodium Channel Mutation in the Copepod Acartia hudsonica to Paralytic Shellfish Toxins (PST)

PubMed Central

Finiguerra, Michael; Avery, David E.; Dam, Hans G.

2015-01-01

The marine copepod Acartia hudsonica was shown to be adapted to dinoflagellate prey, Alexandrium fundyense, which produce paralytic shellfish toxins (PST). Adaptation to PSTs in other organisms is caused by a mutation in the sodium channel. Recently, a mutation in the sodium channel in A. hudsonica was found. In this study, we rigorously tested for advantages, costs, and trade-offs associated with the mutant isoform of A. hudsonica under toxic and non-toxic conditions. We combined fitness with wild-type: mutant isoform ratio measurements on the same individual copepod to test our hypotheses. All A. hudsonica copepods express both the wild-type and mutant sodium channel isoforms, but in different proportions; some individuals express predominantly mutant (PMI) or wild-type isoforms (PWI), while most individuals express relatively equal amounts of each (EI). There was no consistent pattern of improved performance as a function of toxin dose for egg production rate (EPR), ingestion rate (I), and gross growth efficiency (GGE) for individuals in the PMI group relative to individuals in the PWI expression group. Neither was there any evidence to indicate a fitness benefit to the mutant isoform at intermediate toxin doses. No clear advantage under toxic conditions was associated with the mutation. Using a mixed-diet approach, there was also no observed relationship between individual wild-type: mutant isoform ratios and among expression groups, on both toxic and non-toxic diets, for eggs produced over three days. Lastly, expression of the mutant isoform did not mitigate the negative effects of the toxin. That is, the reductions in EPR from a toxic to non-toxic diet for copepods were independent of expression groups. Overall, the results did not support our hypotheses; the mutant sodium channel isoform does not appear to be related to adaptation to PST in A. hudsonica. Other potential mechanisms responsible for the adaptation are discussed. PMID:26075900

QSAR-Based Models for Designing Quinazoline/Imidazothiazoles/Pyrazolopyrimidines Based Inhibitors against Wild and Mutant EGFR

PubMed Central

Chauhan, Jagat Singh; Dhanda, Sandeep Kumar; Singla, Deepak; Agarwal, Subhash M.; Raghava, Gajendra P. S.

2014-01-01

Overexpression of EGFR is responsible for causing a number of cancers, including lung cancer as it activates various downstream signaling pathways. Thus, it is important to control EGFR function in order to treat the cancer patients. It is well established that inhibiting ATP binding within the EGFR kinase domain regulates its function. The existing quinazoline derivative based drugs used for treating lung cancer that inhibits the wild type of EGFR. In this study, we have made a systematic attempt to develop QSAR models for designing quinazoline derivatives that could inhibit wild EGFR and imidazothiazoles/pyrazolopyrimidines derivatives against mutant EGFR. In this study, three types of prediction methods have been developed to design inhibitors against EGFR (wild, mutant and both). First, we developed models for predicting inhibitors against wild type EGFR by training and testing on dataset containing 128 quinazoline based inhibitors. This dataset was divided into two subsets called wild_train and wild_valid containing 103 and 25 inhibitors respectively. The models were trained and tested on wild_train dataset while performance was evaluated on the wild_valid called validation dataset. We achieved a maximum correlation between predicted and experimentally determined inhibition (IC50) of 0.90 on validation dataset. Secondly, we developed models for predicting inhibitors against mutant EGFR (L858R) on mutant_train, and mutant_valid dataset and achieved a maximum correlation between 0.834 to 0.850 on these datasets. Finally, an integrated hybrid model has been developed on a dataset containing wild and mutant inhibitors and got maximum correlation between 0.761 to 0.850 on different datasets. In order to promote open source drug discovery, we developed a webserver for designing inhibitors against wild and mutant EGFR along with providing standalone (http://osddlinux.osdd.net/) and Galaxy (http://osddlinux.osdd.net:8001) version of software. We hope our webserver (http://crdd.osdd.net/oscadd/ntegfr/) will play a vital role in designing new anticancer drugs. PMID:24992720

Genetics Home Reference: von Hippel-Lindau syndrome

MedlinePlus

... more common in particular ethnic groups? Genetic Changes Mutations in the VHL gene cause von Hippel-Lindau ... dividing too rapidly or in an uncontrolled way. Mutations in this gene prevent production of the VHL ...

Netzformen und VDE-Bestimmungen

NASA Astrophysics Data System (ADS)

Bernstein, Herbert

Der Verband Deutscher Elektrotechniker (VDE) hat eine Reihe von Vorschriften ausgearbeitet, die dem Schutz von Leben und Sachen beim Umgang mit elektrischer Energie dienen. Besonders wichtig sind die in den VDE-Bestimmungen 0100 und 0411 festgelegten Vorschriften.

Individuelle Templates für Rekonstruktionen des linken Herzventrikels

NASA Astrophysics Data System (ADS)

Feder, Stefan; Falk, Volkmar; Gutberiet, Matthias; Bartz, Dirk

Bei krankhaften Vergrößerungen des linken Herzventrikels kann eine chirurgische Ventrikelrekonstruktion zur Verbesserung der Herzleistung beitragen. Die dabei erstellte Ventrikelgeometrie ist von entscheidender Bedeutung. Diese Studie befasst sich mit der computerbasierten Planung von individuellen Schablonen (Templates) für Ventrikelrekonstruktionen. Ziel ist es aus Cardio-CT-Daten, präoperativ, patientenindividuelle 3D-Modelle für Ventrikeltemplates zu erstellen. Hierfür wird aus CT-Daten der linksventrikuläre Blutpool segmentiert und daraus das Ventrikeltemplate modelliert. Dies geschieht anhand von zwei Kriterien: dem physiologischen Ventrikelfüllungsvolumen und der hämodynamisch günstigen ellipsoiden Form. Es konnten 20 3D-Templatemodelle mit einem durchschnittlichen Volumen von 144 ml erstellt werden. Die ellipsoide Form konnte durch manuelle Modellierung erreicht werden. Der Nachweis verbesserter Operationsergebnisse muss in nachfolgenden klinischen Studien erbracht werden.

Measurements in Quantum Mechanics and von NEUMANN's Model

NASA Astrophysics Data System (ADS)

Mello, Pier A.; Johansen, Lars M.

2010-12-01

Many textbooks on Quantum Mechanics are not very precise as to the meaning of making a measurement: as a consequence, they frequently make assertions which are not based on a dynamical description of the measurement process. A model proposed by von Neumann allows a dynamical description of measurement in Quantum Mechanics, including the measuring instrument in the formalism. In this article we apply von Neumann's model to illustrate the measurement of an observable by means of a measuring instrument and show how various results, which are sometimens postulated without a dynamical basis, actually emerge. We also investigate the more complex, intriguing and fundamental problem of two successive measurements in Quantum Mechanics, extending von Neumann's model to two measuring instruments. We present a description which allows obtaining, in a unified way, various results that have been given in the literature.

The astronomer of the duchess -- Life and work of Franz Xaver von Zach 1754-1832. (German Title: Der Astronom der Herzogin -- Leben und Werk von Franz Xaver von Zach 1754-1832)

NASA Astrophysics Data System (ADS)

Brosche, Peter

The astronomer, geodesist, geographer and historian of science Franz Xaver von Zach (1754-1832) lived and worked in several European countries. Duke Ernst II of Saxe-Gotha-Altenburg appointed him as the founding scientist of his Seeberg Observatory. This was the place of his strongest activity. Why should we have an interest in him today? There is a rational and an emotional answer. First, he has rendered organisational services to his sciences which are equivalent to a great scientific achievement. Second, Zach was a very colourful character, travelled across many states in a time of radical changes and had connections with many colleagues and public figures. Images from his life therefore provide outlooks, insights and relations.

An efficient screen for peroxisome-deficient mutants of Pichia pastoris.

PubMed Central

Liu, H; Tan, X; Veenhuis, M; McCollum, D; Cregg, J M

1992-01-01

We describe a rapid and efficient screen for peroxisome-deficient (per) mutants in the yeast Pichia pastoris. The screen relies on the unusual ability of P. pastoris to grow on two carbon sources, methanol and oleic acid, both of which absolutely require peroxisomes to be metabolized. A collection of 280 methanol utilization-defective (Mut-) P. pastoris mutants was isolated, organized into 46 complementation groups, and tested for those that were also oleate-utilization defective (Out-) but still capable of growth on ethanol and glucose. Mutants in 10 groups met this phenotypic description, and 8 of these were observed by electron microscopy to be peroxisome deficient (Per-). In each per mutant, Mut-, Out-, and Per- phenotypes were tightly linked and therefore were most likely due to a mutation at a single locus. Subcellular fractionation experiments indicated that the peroxisomal marker enzyme catalase was mislocalized to the cytosol in both methanol- and oleate-induced cultures of the mutants. In contrast, alcohol oxidase, a peroxisomal methanol utilization pathway enzyme, was virtually absent from per mutant cells. The relative ease of per mutant isolation in P. pastoris, in conjunction with well-developed procedures for its molecular and genetic manipulation, makes this organism an attractive system for studies on peroxisome biogenesis. Images PMID:1629154

Genetic control of enhanced mutability of mitochondrial DNA and gamma-ray sensitivity in Saccharomyces cerevisiae.

PubMed Central

Foury, F; Goffeau, A

1979-01-01

Five nuclear mutants enhancing the spontaneous mutation rate of mtDNA have been isolated in Saccharomyces cerevisiae. These mutators fall into five complementation groups and are located at five genetic loci different from rad50 to rad57 loci. Three mutants (gam1, gam2, and gam4), insensitive or weakly sensitive to gamma-rays, exhibit increased frequency of spontaneous production of mutants with large deletions of the mtDNA (p-) and of all tested mitochondrial drug-resistant mutants. Two other mutants (gam3 and gam5), highly sensitive to gamma-rays, increase only the mutation rate of particular alleles of the mtDNA. The mutant gam5 enhances only the production of p- and erythromycin-resistant clones. The mutant gam3 exhibits an enhanced rate of oligomycin-resistant clones as well as a collateral increase of nuclear mutability. The existence of gam3 and gam5 mutants indicates that at least two common steps control both nuclear DNA repair and the mutability of particular alleles of the mtDNA. However, the general spontaneous mutability of the mtDNA includes at least three steps not involved in the repair of nuclear DNA, as revealed by the gam1, gam2, and gam4 mutations. PMID:392521

Construction of Signature-tagged Mutant Library in Mesorhizobium loti as a Powerful Tool for Functional Genomics

PubMed Central

Shimoda, Yoshikazu; Mitsui, Hisayuki; Kamimatsuse, Hiroko; Minamisawa, Kiwamu; Nishiyama, Eri; Ohtsubo, Yoshiyuki; Nagata, Yuji; Tsuda, Masataka; Shinpo, Sayaka; Watanabe, Akiko; Kohara, Mitsuyo; Yamada, Manabu; Nakamura, Yasukazu; Tabata, Satoshi; Sato, Shusei

2008-01-01

Rhizobia are nitrogen-fixing soil bacteria that establish endosymbiosis with some leguminous plants. The completion of several rhizobial genome sequences provides opportunities for genome-wide functional studies of the physiological roles of many rhizobial genes. In order to carry out genome-wide phenotypic screenings, we have constructed a large mutant library of the nitrogen-fixing symbiotic bacterium, Mesorhizobium loti, by transposon mutagenesis. Transposon insertion mutants were generated using the signature-tagged mutagenesis (STM) technique and a total of 29 330 independent mutants were obtained. Along with the collection of transposon mutants, we have determined the transposon insertion sites for 7892 clones, and confirmed insertions in 3680 non-redundant M. loti genes (50.5% of the total number of M. loti genes). Transposon insertions were randomly distributed throughout the M. loti genome without any bias toward G+C contents of insertion target sites and transposon plasmids used for the mutagenesis. We also show the utility of STM mutants by examining the specificity of signature tags and test screenings for growth- and nodulation-deficient mutants. This defined mutant library allows for genome-wide forward- and reverse-genetic functional studies of M. loti and will serve as an invaluable resource for researchers to further our understanding of rhizobial biology. PMID:18658183

Isolation of Temperature-Sensitive Mutants of Arabidopsis thaliana That Are Defective in the Redifferentiation of Shoots.

PubMed Central

Yasutani, I.; Ozawa, S.; Nishida, T.; Sugiyama, M.; Komamine, A.

1994-01-01

Three temperature-sensitive mutants of Arabidopsis thaliana that were defective in the redifferentiation of shoots were isolated as tools for the study of organogenesis. M3 lines were constructed by harvesting M3 seeds separately from each M2 plant. Comparative examination of shoot redifferentiation in root explants of 2700 M3 lines at 22[deg]C (permissive temperature) and at 27[deg]C (restrictive temperature) led to the identification of seven temperature-sensitive mutant lines. Genetic tests of three of the seven mutant lines indicated that temperature-sensitive redifferentiation of shoots in these three lines resulted from single, nuclear, recessive mutations in three different genes, designated SRD1, SRD2, and SRD3. The morphology of root explants of srd mutants cultured at the restrictive temperature suggests that the products of these SRD genes function at different stages of the redifferentiation of shoots. PMID:12232244

Decrease of 3243 A→G mtDNA Mutation from Blood in MELAS Syndrome: A Longitudinal Study

PubMed Central

Rahman, S.; Poulton, J.; Marchington, D.; Suomalainen, A.

2001-01-01

It is widely held that changes in the distribution of mutant mtDNAs underlie the progressive nature of mtDNA diseases, but there are few data documenting such changes. We compared the levels of 3243 A→G mutant mtDNA in blood at birth from Guthrie cards and at the time of diagnosis in a blood DNA sample from patients with mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS) syndrome. Paired blood DNA samples separated by 9–19 years were obtained from six patients with MELAS. Quantification of mutant load, by means of a solid-phase minisequencing technique, demonstrated a decline (range 12%–29%) in the proportion of mutant mtDNA in all cases (P=.0015, paired t-test). These results suggest that mutant mtDNA is slowly selected from rapidly dividing blood cells in MELAS. PMID:11085913

Analysis of Mycobacterium avium subspecies paratuberculosis mutant libraries reveals loci-dependent transposition biases and strategies to novel mutant discovery

USDA-ARS?s Scientific Manuscript database

Mycobacterium avium subsp. paratuberculosis (MAP), the etiologic agent of Johne’s disease, is one of the most important bacterial pathogens in ruminants. The lack of efficacious control measures demands a thorough understanding of MAP pathogenesis to develop new vaccines and diagnostic tests. The ge...

Production of astaxanthin from cellulosic biomass sugars by mutants of the yeast Phaffia rhodozyma

USDA-ARS?s Scientific Manuscript database

Astaxanthin is a carotenoid of high value to the aquaculture, nutraceutical, and pharmaceutical industries. Three mutant strains of the astaxanthin-producing yeast Phaffia rhodozyma, which were derived from the parent strain ATCC 24202 (UCD 67-210) and designated JTM166, JTM185, and SSM19, were test...

Drosophila Mgr, a Prefoldin subunit cooperating with von Hippel Lindau to regulate tubulin stability

PubMed Central

Delgehyr, Nathalie; Wieland, Uta; Rangone, Hélène; Pinson, Xavier; Mao, Guojie; Dzhindzhev, Nikola S.; McLean, Doris; Riparbelli, Maria G.; Llamazares, Salud; Callaini, Giuliano; Gonzalez, Cayetano; Glover, David M.

2012-01-01

Mutations in Drosophila merry-go-round (mgr) have been known for over two decades to lead to circular mitotic figures and loss of meiotic spindle integrity. However, the identity of its gene product has remained undiscovered. We now show that mgr encodes the Prefoldin subunit counterpart of human von Hippel Lindau binding-protein 1. Depletion of Mgr from cultured cells also leads to formation of monopolar and abnormal spindles and centrosome loss. These phenotypes are associated with reductions of tubulin levels in both mgr flies and mgr RNAi-treated cultured cells. Moreover, mgr spindle defects can be phenocopied by depleting β-tubulin, suggesting Mgr function is required for tubulin stability. Instability of β-tubulin in the mgr larval brain is less pronounced than in either mgr testes or in cultured cells. However, expression of transgenic β-tubulin in the larval brain leads to increased tubulin instability, indicating that Prefoldin might only be required when tubulins are synthesized at high levels. Mgr interacts with Drosophila von Hippel Lindau protein (Vhl). Both proteins interact with unpolymerized tubulins, suggesting they cooperate in regulating tubulin functions. Accordingly, codepletion of Vhl with Mgr gives partial rescue of tubulin instability, monopolar spindle formation, and loss of centrosomes, leading us to propose a requirement for Vhl to promote degradation of incorrectly folded tubulin in the absence of functional Prefoldin. Thus, Vhl may play a pivotal role: promoting microtubule stabilization when tubulins are correctly folded by Prefoldin and tubulin destruction when they are not. PMID:22451918

Object-color-signal prediction using wraparound Gaussian metamers.

PubMed

Mirzaei, Hamidreza; Funt, Brian

2014-07-01

Alexander Logvinenko introduced an object-color atlas based on idealized reflectances called rectangular metamers in 2009. For a given color signal, the atlas specifies a unique reflectance that is metameric to it under the given illuminant. The atlas is complete and illuminant invariant, but not possible to implement in practice. He later introduced a parametric representation of the object-color atlas based on smoother "wraparound Gaussian" functions. In this paper, these wraparound Gaussians are used in predicting illuminant-induced color signal changes. The method proposed in this paper is based on computationally "relighting" that reflectance to determine what its color signal would be under any other illuminant. Since that reflectance is in the metamer set the prediction is also physically realizable, which cannot be guaranteed for predictions obtained via von Kries scaling. Testing on Munsell spectra and a multispectral image shows that the proposed method outperforms the predictions of both those based on von Kries scaling and those based on the Bradford transform.

Characterization of phase properties and deformation in ferritic-austenitic duplex stainless steels by nanoindentation and finite element method

DOE PAGES

Schwarm, Samuel C.; Kolli, R. Prakash; Aydogan, Eda; ...

2016-11-03

The phase properties and deformation behavior of the δ–ferrite and γ–austenite phases of CF–3 and CF–8 cast duplex stainless steels were characterized by nanoindentation and microstructure-based finite element method (FEM) models. We evaluated the elastic modulus of each phase and the results indicate that the mean elastic modulus of the δ–ferrite phase is greater than that of the γ–austenite phase, and the mean nanoindentation hardness values of each phase are approximately the same. Furthermore, the elastic FEM model results illustrate that greater von Mises stresses are located within the δ–ferrite phase, while greater von Mises strains are located in themore » γ–austenite phase in response to elastic deformation. The elastic moduli calculated by FEM agree closely with those measured by tensile testing. Finally, the plastically deformed specimens exhibit an increase in misorientation, deformed grains, and subgrain structure formation as measured by electron backscatter diffraction (EBSD).« less

Characterization of phase properties and deformation in ferritic-austenitic duplex stainless steels by nanoindentation and finite element method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwarm, Samuel C.; Kolli, R. Prakash; Aydogan, Eda

The phase properties and deformation behavior of the δ–ferrite and γ–austenite phases of CF–3 and CF–8 cast duplex stainless steels were characterized by nanoindentation and microstructure-based finite element method (FEM) models. We evaluated the elastic modulus of each phase and the results indicate that the mean elastic modulus of the δ–ferrite phase is greater than that of the γ–austenite phase, and the mean nanoindentation hardness values of each phase are approximately the same. Furthermore, the elastic FEM model results illustrate that greater von Mises stresses are located within the δ–ferrite phase, while greater von Mises strains are located in themore » γ–austenite phase in response to elastic deformation. The elastic moduli calculated by FEM agree closely with those measured by tensile testing. Finally, the plastically deformed specimens exhibit an increase in misorientation, deformed grains, and subgrain structure formation as measured by electron backscatter diffraction (EBSD).« less

A learnable parallel processing architecture towards unity of memory and computing

NASA Astrophysics Data System (ADS)

Li, H.; Gao, B.; Chen, Z.; Zhao, Y.; Huang, P.; Ye, H.; Liu, L.; Liu, X.; Kang, J.

2015-08-01

Developing energy-efficient parallel information processing systems beyond von Neumann architecture is a long-standing goal of modern information technologies. The widely used von Neumann computer architecture separates memory and computing units, which leads to energy-hungry data movement when computers work. In order to meet the need of efficient information processing for the data-driven applications such as big data and Internet of Things, an energy-efficient processing architecture beyond von Neumann is critical for the information society. Here we show a non-von Neumann architecture built of resistive switching (RS) devices named “iMemComp”, where memory and logic are unified with single-type devices. Leveraging nonvolatile nature and structural parallelism of crossbar RS arrays, we have equipped “iMemComp” with capabilities of computing in parallel and learning user-defined logic functions for large-scale information processing tasks. Such architecture eliminates the energy-hungry data movement in von Neumann computers. Compared with contemporary silicon technology, adder circuits based on “iMemComp” can improve the speed by 76.8% and the power dissipation by 60.3%, together with a 700 times aggressive reduction in the circuit area.

Untersuchung der Störwirkung von LTE auf SRD Anwendungen bei 868 MHz

NASA Astrophysics Data System (ADS)

Welpot, M.; Wunderlich, S.; Gaspard, I.

2014-11-01

Moderne Hausautomatisierungssysteme, Alarmanlagen oder auch Funk-Zugangssysteme in Haus und Automobil setzen auf frei nutzbare Frequenzen in ISM/SRD-Bändern. Die rasante Zunahme an privaten und kommerziell genutzten Applikationen im SRD-Band bei 868 MHz und der Ausbau der LTE-Mobilfunknetze im Frequenzbereich unterhalb von 1 GHz ("Digital Dividend") wirft zunehmend die Frage nach der Funkverträglichkeit dieser Systeme untereinander auf. Während die SRD-Funkmodule auf eine geringe Sendeleistung von ~ +14 dBm beschränkt sind (Ralf and Thomas, 2009), beträgt die maximale LTE-Sendeleistung im Uplink nach (ETSI-Norm, 2011) +23 dBm. Zusammen mit der Einführung von LTE im Frequenzbereich unterhalb 1 GHz als DSL-Ersatz vor allem in ländlichen Gebieten, ergibt sich damit als mögliches Störszenario, dass durch die Aussendung des LTE-Endgerätes im Bereich von ca. 850 MHz die SRD-Funkverbindungen bei 868 MHz insbesondere dann gestört werden, wenn die Antennen beider Funksysteme räumlich nahe zueinander angeordnet sind und folglich nur eine geringe zusätzliche Entkopplung der Systeme bieten. In der vorliegenden Arbeit wird das LTE-Störpotential auf SRD-Empfänger praxisnah untersucht.

Beyond victimhood. The struggle of Munich anatomist Titus von Lanz during National Socialism.

PubMed

Schütz, Mathias; Waschke, Jens; Marckmann, Georg; Steger, Florian

2015-09-01

The article analyzes the life and career of the anatomist Titus von Lanz (1897-1967) of Munich focusing on the period of National Socialism (NS). Von Lanz lost his position as an associate professor at the Anatomical Institute of Munich University because of his marriage to a "half-Jewish" woman in 1938. In contrast to most of his colleagues affected by National Socialist measures, von Lanz had opportunities to save his career and made extensive use of them. His story is that of a complicated struggle for the continuation of his work, involving a wide range of supporters from prestigious physicians to high-ranking National Socialist officials as well as the alienation of his colleagues at the Munich department of anatomy. The article tries to clarify these developments through the presentation of his social background, his supporters, his enemies, the research he conducted during NS and von Lanz' own remembrance of these developments from the post-war period. It aims at laying out a critical appreciation of his motives and actions, thereby contributing to the understanding of individual behavior of anatomists under NS. Copyright © 2015 Elsevier GmbH. All rights reserved.

A learnable parallel processing architecture towards unity of memory and computing.

PubMed

Li, H; Gao, B; Chen, Z; Zhao, Y; Huang, P; Ye, H; Liu, L; Liu, X; Kang, J

2015-08-14

Developing energy-efficient parallel information processing systems beyond von Neumann architecture is a long-standing goal of modern information technologies. The widely used von Neumann computer architecture separates memory and computing units, which leads to energy-hungry data movement when computers work. In order to meet the need of efficient information processing for the data-driven applications such as big data and Internet of Things, an energy-efficient processing architecture beyond von Neumann is critical for the information society. Here we show a non-von Neumann architecture built of resistive switching (RS) devices named "iMemComp", where memory and logic are unified with single-type devices. Leveraging nonvolatile nature and structural parallelism of crossbar RS arrays, we have equipped "iMemComp" with capabilities of computing in parallel and learning user-defined logic functions for large-scale information processing tasks. Such architecture eliminates the energy-hungry data movement in von Neumann computers. Compared with contemporary silicon technology, adder circuits based on "iMemComp" can improve the speed by 76.8% and the power dissipation by 60.3%, together with a 700 times aggressive reduction in the circuit area.

[out of scope].

PubMed

Siegmund-Schultze, Reinhard

2008-01-01

The paper discusses several still unsettled and not systematically investigated questions concerning the situation of Jewish scientists, among them mathematicians, in the Republic of Weimar. Contemporary statements by the well-known leftist and liberal journalists Carl von Ossietzky (1932) and Rudolf Olden (1934) are used to describe the general political situation. A wide-spread feeling of a social and political crisis and changes and perturbations in international scientific communication provide explanatory background for the conditions within academia in the 1920s. A comparison of appointments of Jewish mathematicians to full professorships before and after World War I does not give significant differences. Attitudes of Jewish mathematicians such as Felix Bernstein, Richard Courant, Emil Julius Gumbel, Edmund Landau, Richard von Mises, Johann von Neumann and Adolf A. Fraenkel, but also of non-Jewish mathematicians such as Felix Klein, Walther von Dyck and Theodor Vahlen will be discussed, providing some unpublished material. One statement by Felix Klein (1920), which shows his undecided stance with respect to the problem of anti-Semitism, and an excerpt from Richard von Mises' diary (1933), where he reflects on his status as a Jewish mathematician and as a refugee, are particularly valuable as points of reference for necessary further research.

Measuring Changes in Tactile Sensitivity in the Hind Paw of Mice Using an Electronic von Frey Apparatus

PubMed Central

Martinov, Tijana; Mack, Madison; Sykes, Akilah; Chatterjea, Devavani

2013-01-01

Measuring inflammation-induced changes in thresholds of hind paw withdrawal from mechanical pressure is a useful technique to assess changes in pain perception in rodents. Withdrawal thresholds can be measured first at baseline and then following drug, venom, injury, allergen, or otherwise evoked inflammation by applying an accurate force on very specific areas of the skin. An electronic von Frey apparatus allows precise assessment of mouse hind paw withdrawal thresholds that are not limited by the available filament sizes in contrast to classical von Frey measurements. The ease and rapidity of measurements allow for incorporation of assessment of tactile sensitivity outcomes in diverse models of rapid-onset inflammatory and neuropathic pain as multiple measurements can be taken within a short time period. Experimental measurements for individual rodent subjects can be internally controlled against individual baseline responses and exclusion criteria easily established to standardize baseline responses within and across experimental groups. Thus, measurements using an electronic von Frey apparatus represent a useful modification of the well-established classical von Frey filament-based assays for rodent mechanical allodynia that may also be applied to other nonhuman mammalian models. PMID:24378519

Analysis of a Partial Male-Sterile Mutant of Arabidopsis thaliana Isolated from a Low-Energy Argon Ion Beam Mutagenized Pool

NASA Astrophysics Data System (ADS)

Xu, Min; Bian, Po; Wu, Yuejin; Yu, Zengliang

2008-04-01

A screen for Arabidopsis fertility mutants, mutagenized by low-energy argon ion beam, yielded two partial male-sterile mutants tc243-1 and tc243-2 which have similar phenotypes. tc243-2 was investigated in detail. The segregation ratio of the mutant phenotypes in the M2 pools suggested that mutation behaved as single Mendelian recessive mutations. tc243 showed a series of mutant phenotypes, among which partial male-sterile was its striking mutant characteristic. Phenotype analysis indicates that there are four factors leading to male sterility. a. Floral organs normally develop inside the closed bud, but the anther filaments do not elongate sufficiently to position the locules above the stigma at anthesis. b. The anther locules do not dehisce at the time of flower opening (although limited dehiscence occurs later). c. Pollens of mutant plants develop into several types of pollens at the trinucleated stage, as determined by staining with DAPI (4',6-diamidino-2-phenylindole), which shows a variable size, shape and number of nucleus. d. The viability of pollens is lower than that of the wild type on the germination test in vivo and vitro.

A Search for a General Phenomenon of Adaptive Mutability

PubMed Central

Galitski, T.; Roth, J. R.

1996-01-01

The most prominent systems for the study of adaptive mutability depend on the specialized activities of genetic elements like bacteriophage Mu and the F plasmid. Searching for general adaptive mutability, we have investigated the behavior of Salmonella typhimurium strains with chromosomal lacZ mutations. We have studied 30 revertible nonsense, missense, frameshift, and insertion alleles. One-third of the mutants produced >=10 late revertant colonies (appearing three to seven days after plating on selective medium). For the prolific mutants, the number of late revertants showed rank correlation with the residual β-galactosidase activity; for the same mutants, revertant number showed no correlation with the nonselective reversion rate (from fluctuation tests). Leaky mutants, which grew slowly on selective medium, produced late revertants whereas tight nongrowing mutants generally did not produce late revertants. However, the number of late revertants was not proportional to residual growth. Using total residual growth and the nonselective reversion rate, the expected number of late revertants was calculated. For several leaky mutants, the observed revertant number exceeded the expected number. We suggest that excess late revertants from these mutants arise from general adaptive mutability available to any chromosomal gene. PMID:8725216

Dr. von Braun Tours the North American Aviation

NASA Technical Reports Server (NTRS)

1962-01-01

Dr. Wernher von Braun, Director of the Marshall Space Flight Center (MSFC), during his tour of the Space information Division of North American Aviation (NAA) in Downey, California, where the Saturn SII stage was developed.

Dr. von Braun tours the North American Aviation

NASA Technical Reports Server (NTRS)

1962-01-01

Dr. Wernher von Braun, Director of the Marshall Space Flight Center (MSFC), during his tour of the Space Information Division of North American Aviation (NAA) in Downey, California, where the Saturn SII stage was developed.

Wernher von Braun

NASA Image and Video Library

1959-01-01

Marshall Space Flight Center Director Wernher von Braun presents General J.B. Medaris with a new golf bag. General Medaris, (left) was a Commander of the Army Ballistic Missile Agency (ABMA) in Redstone Arsenal, Alabama during 1955 to 1958.

Assessment of Creep Deformation, Damage, and Rupture Life of 304HCu Austenitic Stainless Steel Under Multiaxial State of Stress

NASA Astrophysics Data System (ADS)

Sahoo, K. C.; Goyal, Sunil; Parameswaran, P.; Ravi, S.; Laha, K.

2018-03-01

The role of the multiaxial state of stress on creep deformation and rupture behavior of 304HCu austenitic stainless steel was assessed by performing creep rupture tests on both smooth and notched specimens of the steel. The multiaxial state of stress was introduced by incorporating circumferential U-notches of different root radii ranging from 0.25 to 5.00 mm on the smooth specimens of the steel. Creep tests were carried out at 973 K over the stress range of 140 to 220 MPa. In the presence of notch, the creep rupture strength of the steel was found to increase with the associated decrease in rupture ductility. Over the investigated stress range and notch sharpness, the strengthening was found to increase drastically with notch sharpness and tended toward saturation. The fractographic studies revealed the mixed mode of failure consisting of transgranular dimples and intergranular creep cavitation for shallow notches, whereas the failure was predominantly intergranular for relatively sharper notches. Detailed finite element analysis of stress distribution across the notch throat plane on creep exposure was carried out to assess the creep failure of the material in the presence of notch. The reduction in von-Mises stress across the notch throat plane, which was greater for sharper notches, increased the creep rupture strength of the material. The variation in fracture behavior of the material in the presence of notch was elucidated based on the von-Mises, maximum principal, and hydrostatic stresses. Electron backscatter diffraction analysis of creep strain distribution across the notch revealed localized creep straining at the notch root for sharper notches. A master curve for predicting creep rupture life under the multiaxial state of stress was generated considering the representative stress having contributions from both the von-Mises and principal stress components of the stress field in the notch throat plane. Rupture ductility was also predicted based on the multiaxial state of stress.

Cellular evidence for selfish spermatogonial selection in aged human testes.

PubMed

Maher, G J; Goriely, A; Wilkie, A O M

2014-05-01

Owing to a recent trend for delayed paternity, the genomic integrity of spermatozoa of older men has become a focus of increased interest. Older fathers are at higher risk for their children to be born with several monogenic conditions collectively termed paternal age effect (PAE) disorders, which include achondroplasia, Apert syndrome and Costello syndrome. These disorders are caused by specific mutations originating almost exclusively from the male germline, in genes encoding components of the tyrosine kinase receptor/RAS/MAPK signalling pathway. These particular mutations, occurring randomly during mitotic divisions of spermatogonial stem cells (SSCs), are predicted to confer a selective/growth advantage on the mutant SSC. This selective advantage leads to a clonal expansion of the mutant cells over time, which generates mutant spermatozoa at levels significantly above the background mutation rate. This phenomenon, termed selfish spermatogonial selection, is likely to occur in all men. In rare cases, probably because of additional mutational events, selfish spermatogonial selection may lead to spermatocytic seminoma. The studies that initially predicted the clonal nature of selfish spermatogonial selection were based on DNA analysis, rather than the visualization of mutant clones in intact testes. In a recent study that aimed to identify these clones directly, we stained serial sections of fixed testes for expression of melanoma antigen family A4 (MAGEA4), a marker of spermatogonia. A subset of seminiferous tubules with an appearance and distribution compatible with the predicted mutant clones were identified. In these tubules, termed 'immunopositive tubules', there is an increased density of spermatogonia positive for markers related to selfish selection (FGFR3) and SSC self-renewal (phosphorylated AKT). Here we detail the properties of the immunopositive tubules and how they relate to the predicted mutant clones, as well as discussing the utility of identifying the potential cellular source of PAE mutations. © 2013 American Society of Andrology and European Academy of Andrology.

Aufnahme, Analyse und Visualisierung von Bewegungen nativer Herzklappen in-vitro

NASA Astrophysics Data System (ADS)

Weiß, Oliver; Friedl, Sven; Kondruweit, Markus; Wittenberg, Thomas

Die hohe Zahl an Transplantationen von Herzklappen und viele nötige Re-Operationen machen eine detaillierte Analyse der Strömungen und Klappenbewegungen klinisch interessant. Ein neuer Ansatz ist hierbei der Einsatz von Hochgeschwindigkeitskameras um Bewegungsabl äufe der Herzklappen beobachten und auswerten zu können. Die hohen Datenraten erfordern allerdings eine möglichst automatisierte Analyse und möglichst komprimierte Darstellung des Schwingungsverhaltens. In dieser Arbeit wird ein Ansatz vorgestellt, bei dem Bewegungen nativer Herzklappen in-vitro aufgenommen, analysiert und kompakt visualisiert werden.

GPU-basierte Smart Visibility Techniken für die Planung von Tumor-Operationen

NASA Astrophysics Data System (ADS)

Tietjen, Christian; Kubisch, Christoph; Hiller, Stefan; Preim, Bernhard

Bei der Planung von Tumoroperationen ist die Einschätzung von Abständen und Infiltrationen zu vitalen Strukturen wichtig. Im Bereich der medizinischen Visualisierung wurden hierfür bereits zahlreiche Techniken entwickelt, die unter dem Begriff Smart Visibility zusammengefasst werden. Zu diesen zählen Ghost Views und Section Views. In diesem Beitrag wird eine GPU-basierte Realisierung dieser Techniken für polygonale Daten vorgestellt. Die Parametrisierung der Techniken erfolgt automatisch, um einen klinischen Einsatz ermöglichen zu können.

Standing Fast: German Defensive Doctrine on the Russian Front During the Second World War.

DTIC Science & Technology

1983-06-03

von Kluge, Hitler explained that the demands of other fronts (especially Italy) required the transfer of perhaps ’ b| ’P q . . • .,,, -’ ’’’ ’’’ h ...historians such as Heinrich von Treitschke , who regarded past military glory as the wellspring of German nationalism. One of the most onerous aspects of the...Prince Wilhelm of Germany , !.L War Experiences (London: Hurst * and Blackett, 1923), p. 267. " 8See, for example, "General Von Maur’s Memorandum on

Recurrent haematomas of the thigh: a case of von Willebrand's disease presenting to a sports clinic

PubMed Central

Owens, S.; Baglin, T.

2000-01-01

Von Willebrand's disease is a relatively common mild form of haemophilia. It should be suspected in assessing sports injuries when excessive bleeding occurs in response to relatively mild trauma. Those with the disease should remain active but avoid contact sports. They should not take aspirin or non-steroidal anti-inflammatory drugs, which may exacerbate bleeding, and should be given supportive treatment to cover dental extraction, surgery, or significant bleeding episodes. Key Words: von Willebrand's disease; haemophilia; haematoma; sports clinic PMID:10786868

The Influence and Reasons for Acceptance or Rejection of Operational Level Intelligence during the 1914 Marne and 1943 Kursk Campaigns,

DTIC Science & Technology

1988-04-26

J- commander General von Xoltke to send them additional troops instead of ’ following the original Schlieffen Plan. At about the same time another...two Corps were taken from the right wing to counter unexpected Russian success on the Eastern front. As von Xoltke was destroying the Schlieffen Plan...Army. This resulted in von Xoltke ordering a general withdrawal to the line of the Aisne.(17) Thus ended the German bid for a short, glorious war won by

Schaltungsunterlagen

NASA Astrophysics Data System (ADS)

Döring, Peter

Beim Zeichnen von Schaltplänen werden alle zugehörigen Maschinen, Geräte, Schaltteile und Leitungen nicht maßstabsgetreu und der tatsächlichen Ausführung ähnlich gezeichnet, sondern durch genormte graphische Symbole dargestellt. Die Ausführungen in diesem Kapitel sollen dazu eine Hilfestellung geben. Behandelt werden folgende Themen: Wichtige VDE-Bestimmungen; Diagrammdarstellungen; Schaltzeichen nach DIN; Kennzeichnung von elektrischen Betriebsmitteln; Schaltungsunterlagen der Energietechnik; Schaltungsunterlagen der Elektronik; Schaltzeichen für Binäre Elemente; Entwurf von Schaltungen: Einzelplatinen, Gedruckte Schaltungen; Projektierung. Zahlreiche Tabellen und Abbildungen dienen zur Erläuterung.

Kinematic α tensors and dynamo mechanisms in a von Kármán swirling flow.

PubMed

Ravelet, F; Dubrulle, B; Daviaud, F; Ratié, P-A

2012-07-13

We provide experimental and numerical evidence of in-blades vortices in the von Kármán swirling flow. We estimate the associated kinematic α-effect tensor and show that it is compatible with recent models of the von Kármán sodium (VKS) dynamo. We further show that depending on the relative frequency of the two impellers, the dominant dynamo mechanism may switch from α2 to α - Ω dynamo. We discuss some implications of these results for VKS experiments.

'A WONDERFULL MONSTER BORNE IN GERMANY': HAIRY GIRLS IN MEDIEVAL AND EARLY MODERN GERMAN BOOK, COURT AND PERFORMANCE CULTURE.

PubMed

Katritzky, M A

2014-09-24

Human hirsuteness, or pathological hair growth, can be symptomatic of various conditions, including genetic mutation or inheritance, and some cancers and hormonal disturbances. Modern investigations into hirsuteness were initiated by nineteenth-century German physicians. Most early modern European cases of hypertrichosis (genetically determined all-over body and facial hair) involve German-speaking parentage or patronage, and are documented in German print culture. Through the Wild Man tradition, modern historians routinely link early modern reception of historical hypertrichosis cases to issues of ethnicity without, however, recognising early modern awareness of links between temporary hirsuteness and the pathological nexus of starvation and anorexia. Here, four cases of hirsute females are reconsidered with reference to this medical perspective, and to texts and images uncovered by my current research at the Herzog August Library and German archives. One concerns an Italian girl taken to Prague in 1355 by the Holy Roman Empress, Anna von Schweidnitz. Another focuses on Madeleine and Antonietta Gonzalez, daughters of the 'Wild Man' of Tenerife, documented at German courts in the 1580s. The third and fourth cases consider the medieval bearded Sankt Kümmernis (also known as St Wilgefortis or St Uncumber), and the seventeenth-century Bavarian fairground performer Barbara Urslerin. Krankhafter menschlicher Hirsutismus kann aufgrund unterschiedlicher Ursachen auftreten, zu denen u.a. genetische Veländerungen und Vererbung, verschiedene Krebserkrankungen und hormonelle Störungen gehören. Die moderne Hirsutismus-Forschung ist im 19. Jh. von deutschen Forschern initiiert worden. Die meisten europäischen frühneuzeitlichen Erscheinungen von Hypertrichose (dem genetisch bedingten Haarwuchs am gesamten Körper und im Gesicht) gehen auf deutschsprachige Eltern oder Förderer zurück und sind in Deutschland in den Druck gelangt. Bei Untersuchungen des Motivs des Wilden Mannes zieht die aktuelle geschichtswissenschaftliche Forschung in der Regel Verbindungslinien zwischen der frühneuzeitlichen Wahrnehmung von Hypertrichose-Fällen und Fragen der Ethnizität, ohne jedoch zu beachten, dass in der Frühen Neuzeit die Verbindung zwischen temporärem Hirsutismus und der krankhaften Verknüpfung von Unterernährung und Anorexie bekannt war. Im vorliegenden Beitragwerden vier Fälle von an Hirsutismus erkrankten Frauen neu analysiert, unter Einbezug dieser medizinischen Perspektive und unter Beachtung von Texten und Abbildungen, die meine jüngsten Forschungen in der Herzog August Bibliothek und an deutschen Archiven ans Licht gefördert haben. Die hier betrachteten Fälle betreffen ein italienisches Mädchen, das 1355 von Anna von Schweidnitz, Kaiserin des Hl. Römischen Reichs, nach Prag gebracht wurde; Madeleine und Antonietta Gonzalez, die Töchter des 'Wilden Manns' von Teneriffa, die in den 1580er Jahren an deutschen Höfen bezeugt sind; die bärtige Sankt Kümmernis (Wilgefortis), und die bayerische Jahrmarktkünstlerin Barbara Urslerin.

‘A Wonderfull Monster Borne in Germany’: Hairy Girls in Medieval and Early Modern German Book, Court and Performance Culture*

PubMed Central

Katritzky, MA

2014-01-01

Human hirsuteness, or pathological hair growth, can be symptomatic of various conditions, including genetic mutation or inheritance, and some cancers and hormonal disturbances. Modern investigations into hirsuteness were initiated by nineteenth-century German physicians. Most early modern European cases of hypertrichosis (genetically determined all-over body and facial hair) involve German-speaking parentage or patronage, and are documented in German print culture. Through the Wild Man tradition, modern historians routinely link early modern reception of historical hypertrichosis cases to issues of ethnicity without, however, recognising early modern awareness of links between temporary hirsuteness and the pathological nexus of starvation and anorexia. Here, four cases of hirsute females are reconsidered with reference to this medical perspective, and to texts and images uncovered by my current research at the Herzog August Library and German archives. One concerns an Italian girl taken to Prague in 1355 by the Holy Roman Empress, Anna von Schweidnitz. Another focuses on Madeleine and Antonietta Gonzalez, daughters of the ‘Wild Man’ of Tenerife, documented at German courts in the 1580s. The third and fourth cases consider the medieval bearded Sankt Kümmernis (also known as St Wilgefortis or St Uncumber), and the seventeenth-century Bavarian fairground performer Barbara Urslerin. Krankhafter menschlicher Hirsutismus kann aufgrund unterschiedlicher Ursachen auftreten, zu denen u.a. genetische Veränderungen und Vererbung, verschiedene Krebserkrankungen und hormonelle Störungen gehören. Die moderne Hirsutismus-Forschung ist im 19. Jh. von deutschen Forschern initiiert worden. Die meisten europäischen frühneuzeitlichen Erscheinungen von Hypertrichose (dem genetisch bedingten Haarwuchs am gesamten Körper und im Gesicht) gehen auf deutschsprachige Eltern oder Förderer zurück und sind in Deutschland in den Druck gelangt. Bei Untersuchungen des Motivs des Wilden Mannes zieht die aktuelle geschichtswissenschaftliche Forschung in der Regel Verbindungslinien zwischen der frühneuzeitlichen Wahrnehmung von Hypertrichose-Fällen und Fragen der Ethnizität, ohne jedoch zu beachten, dass in der Frühen Neuzeit die Verbindung zwischen temporärem Hirsutismus und der krankhaften Verknüpfung von Unterernährung und Anorexie bekannt war. Im vorliegenden Beitrag werden vier Fälle von an Hirsutismus erkrankten Frauen neu analysiert, unter Einbezug dieser medizinischen Perspektive und unter Beachtung von Texten und Abbildungen, die meine jüngsten Forschungen in der Herzog August Bibliothek und an deutschen Archiven ans Licht gefördert haben. Die hier betrachteten Fälle betreffen ein italienisches Mädchen, das 1355 von Anna von Schweidnitz, Kaiserin des Hl. Römischen Reichs, nach Prag gebracht wurde; Madeleine und Antonietta Gonzalez, die Töchter des ‘Wilden Manns’ von Teneriffa, die in den 1580er Jahren an deutschen Höfen bezeugt sind; die bärtige Sankt Kümmernis (Wilgefortis), und die bayerische Jahrmarktkünstlerin Barbara Urslerin. PMID:25598545

Characterizing the metatranscriptomic profile of archaeal metabolic genes at deep-sea hydrothermal vents in the Mid-Cayman Rise

NASA Astrophysics Data System (ADS)

Galambos, D.; Reveillaud, J. C.; Anderson, R.; Huber, J. A.

2017-12-01

Deep-sea hydrothermal vent systems host a wide diversity of bacteria, archaea and viruses. Although the geochemical conditions at these vents are well-documented, the relative metabolic activity of microbial lineages, especially among archaea, remains poorly characterized. The deep, slow-spreading Mid-Cayman Rise, which hosts the mafic-influenced Piccard and ultramafic-influenced Von Damm vent fields, allows for the comparison of vent sites with different geochemical characteristics. Previous metagenomic work indicated that despite the distinct geochemistry at Von Damm and Piccard, the functional profile of microbial communities between the two sites was similar. We examined relative metabolic gene activity using a metatranscriptomic analysis and observed functional similarity between Von Damm and Piccard, which is consistent with previous results. Notably, the relative expression of the methyl-coenzyme M reductase (mcr) gene was elevated in both vent fields. Additionally, we analyzed the ratio of RNA expression to DNA abundance of fifteen archaeal metagenome-assembled genomes (MAGs) across the two fields. Previous work showed higher archaeal diversity at Von Damm; our results indicate relatively even expression among archaeal lineages at Von Damm. In contrast, we observed lower archaeal diversity at Piccard, but individual archaeal lineages were very highly expressed; Thermoprotei showed elevated transcriptional activity, which is consistent with higher temperatures and sulfur levels at Piccard. At both Von Damm and Piccard, specific Methanococcus lineages were more highly expressed than others. Future analyses will more closely examine metabolic genes in these Methanococcus MAGs to determine why some lineages are more active at a vent field than others. We will conduct further statistical analyses to determine whether significant differences exist between Von Damm and Piccard and whether there are correlations between geochemical metadata and metabolic gene or archaeal MAG transcription. These efforts will lead to a better understanding of the metabolic characteristics of ancient archaea and the extent to which vent geochemistry influences local microbial metabolic profiles.

Stunden abstract. Der Einsatz von Nachrichten im Leistungskurs "Social Problems" (Class-Hour Plan. The Introduction of News in the Honors Course "Social Problems")

ERIC Educational Resources Information Center

Pegler, Klaus

1977-01-01

Gives a detailed ESL (English as a second language) class-hour plan for using a BBC radio news program on vandalism as a social problem. Teaching goals, teaching materials and methodology are discussed. The working texts are appended; the news tests are available free from the author. (Text is in German.) (IFS/WGA)

Homology-dependent repair is involved in 45S rDNA loss in plant CAF-1 mutants

PubMed Central

Muchová, Veronika; Amiard, Simon; Mozgová, Iva; Dvořáčková, Martina; Gallego, Maria E; White, Charles; Fajkus, Jiří

2015-01-01

Arabidopsis thaliana mutants in FAS1 and FAS2 subunits of chromatin assembly factor 1 (CAF1) show progressive loss of 45S rDNA copies and telomeres. We hypothesized that homology-dependent DNA damage repair (HDR) may contribute to the loss of these repeats in fas mutants. To test this, we generated double mutants by crossing fas mutants with knock-out mutants in RAD51B, one of the Rad51 paralogs of A. thaliana. Our results show that the absence of RAD51B decreases the rate of rDNA loss, confirming the implication of RAD51B-dependent recombination in rDNA loss in the CAF1 mutants. Interestingly, this effect is not observed for telomeric repeat loss, which thus differs from that acting in rDNA loss. Involvement of DNA damage repair in rDNA dynamics in fas mutants is further supported by accumulation of double-stranded breaks (measured as γ-H2AX foci) in 45S rDNA. Occurrence of the foci is not specific for S-phase, and is ATM-independent. While the foci in fas mutants occur both in the transcribed (intranucleolar) and non-transcribed (nucleoplasmic) fraction of rDNA, double fas rad51b mutants show a specific increase in the number of the intranucleolar foci. These results suggest that the repair of double-stranded breaks present in the transcribed rDNA region is RAD51B dependent and that this contributes to rDNA repeat loss in fas mutants, presumably via the single-stranded annealing recombination pathway. Our results also highlight the importance of proper chromatin assembly in the maintenance of genome stability. PMID:25359579

Generation of a Uracil Auxotroph Strain of the Probiotic Yeast Saccharomyces boulardii as a Host for the Recombinant Protein Production

PubMed Central

Hamedi, Hassan; Misaghi, Ali; Modarressi, Mohammad Hossein; Salehi, Taghi Zahraei; Khorasanizadeh, Dorsa; Khalaj, Vahid

2013-01-01

Background Saccharomyces boulardii (S. boulardii) is the best known probiotic yeast. The genetic engineering of this probiotic strain requires the availability of appropriate mutants to accept various gene constructs carrying different selection markers. As the auxotrophy selection markers are under focus, we have generated a ura3 auxotroph mutant of S. boulardii for use in further genetic manipulations. Methods Classical UV mutagenesis was used for the generation of auxotroph mutants. The mutants were selected in the presence of 5-FOA (5-Fluoroorotic acid), uracil and uridine. Uracil auxotrophy phenotype was confirmed by the ability of mutants to grow in the presence of uracil and the lack of growth in the absence of this compound. To test whether the uracil auxotrophy phenotype is due to the inactivation of URA3, the mutants were transformed with a plasmid carrying the gene. An in vitro assay was used for the analysis of acid and bile resistance capacity of these mutants. Results Three mutants were found to be ura3 auxotroph as they were able to grow only in the presence of uracil. When the URA3 gene was added, these mutants were able to grow normally in the absence of uracil. Further in vitro analysis showed that the acid and bile resistance capacity of one of these mutants is intact and similar to the wild type. Conclusion A uracil auxotroph mutant of the probiotic yeast, S. boulardii, was generated and characterized. This auxotroph strain may have potential applications in the production and delivery of the recombinant pharmacuetics into the intestinal lumen. PMID:23626874

Rhodobacter sphaeroides spd mutations allow cytochrome c2-independent photosynthetic growth.

PubMed Central

Rott, M A; Donohue, T J

1990-01-01

In Rhodobacter sphaeroides, cytochrome c2 (cyt c2) is a periplasmic redox protein required for photosynthetic electron transfer. cyt c2-deficient mutants created by replacing the gene encoding the apoprotein for cyt c2 (cycA) with a kanamycin resistance cartridge are photosynthetically incompetent. Spontaneous mutations that suppress this photosynthesis deficiency (spd mutants) arise at a frequency of 1 to 10 in 10(7). We analyzed the cytochrome content of several spd mutants spectroscopically and by heme peroxidase assays. These suppressors lacked detectable cyt c2, but they contained a new soluble cytochrome which was designated isocytochrome c2 (isocyt c2) that was not detectable in either cycA+ or cycA mutant cells. When spd mutants were grown photosynthetically, isocyt c2 was present at approximately 20 to 40% of the level of cyt c2 found in photosynthetically grown wild type cells, and it was found in the periplasm with cytochromes c' and c554. These spd mutants also had several other pleiotropic phenotypes. Although photosynthetic growth rates of the spd mutants were comparable to those of wild-type strains at all light intensities tested, they contained elevated levels of B800-850 pigment-protein complexes. Several spd mutants contained detectable amounts of isocyt c2 under aerobic conditions. Finally, heme peroxidase assays indicated that, under anaerobic conditions, the spd mutants may contain another new cytochrome in addition to isocyt c2. These pleiotropic phenotypes, the frequency at which the spd mutants arise, and the fact that a frameshift mutagen is very effective in generating the spd phenotype suggest that some spd mutants contain a mutation in loci which regulate cytochrome synthesis. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 PMID:2156806

Wernher von Braun

NASA Image and Video Library

1950-01-01

Dr. von Braun stands beside a model of the upper stage (Earth-returnable stage) of the three-stage launch vehicle built for the series of the motion picture productions of space flight produced by Walt Disney in the mid-1950's.

Die Kosmogonie Anton von Zachs.

NASA Astrophysics Data System (ADS)

Brosche, P.

In his "Cosmogenische Betrachtungen" (1804), Anton von Zach rediscovered - probably independently - some aspects of the theories of Kant and Laplace. More originally, he envisaged also the consequences of an era of heavy impacts in the early history of the Earth.

Wernher von Braun

NASA Image and Video Library

1959-01-01

In this picture, Dr. Wernher von Braun, who was serving as Director of the Army Ballistic Missile Agency's (ABMA) Development Operations Division, is shown posed with his Mercedes 220SE automobile in front of Redstone Building 4488, which houses the ABMA.

Inhibitory activity of aspirin on von Willebrand factor-induced platelet aggregation.

PubMed

Homoncik, M; Jilma, B; Eichelberger, B; Panzer, S

2000-09-01

The effect of aspirin (ASA) on vWF induced platelet - platelet interaction is unknown. We therefore tested the response of platelets to von Willebrand factor (vWF) coated beads induced platelet aggregation before and after i.v. and oral ASA. 1000 mg ASA was infused to 10 healthy individuals and after a wash-out period 7 volunteers received 100 mg ASA orally over a period of 11 days. Prior to ASA and in regular intervals thereafter we tested the reactivity to vWF-coated beads to assess platelet adhesion/aggregation and the fade-out time of ASA effects on platelets. Considerable interindividual variability in response to vWF-coated beads was observed, both before ASA and after treatment with ASA. The maximal response to vWF-coated beads (Tmax), the time lag, and the slope of the curve were significantly affected by i.v. ASA, whereas 100 mg of ASA had only inconstant effect on Tmax and slope. The absolute reduction of Tmax after ASA depended on the pre-ASA level, while the percentage of the reduction was similar in all individuals. Thus, platelet aggregation induced by vWF-coated beads is impaired by ASA. Furthermore, our data indicate a large interindividual variability of the response to ASA shortly after treatment induction, which becomes more constant after prolonged treatment.

Hemophilia and von Willebrand's disease: 2. Management. Association of Hemophilia Clinic Directors of Canada.

PubMed Central

1995-01-01

OBJECTIVE: To present current strategies for the treatment of hemophilia and von Willebrand's disease. OPTIONS: Prophylactic and corrective therapy with hemostatic and adjunctive agents: DDAVP (1-desamino-8-D-arginine vasopressin [desmopressin acetate]), recombinant coagulation products (human Factor VIII and human Factor VIIa) or virally inactivated plasma-derived products (high- or ultra-high-purity human Factor VIII or human Factor VIII concentrate containing von Willebrand factor activity, porcine Factor VIII, high-purity human Factor IX, human prothrombin-complex concentrate, human activated prothrombin-complex concentrate), adjunctive antifibrinolytic agents, topical thrombin and fibrin sealant. The induction of immune tolerance in patients in whom inhibitors develop should also be considered. OUTCOMES: Morbidity and quality of life associated with bleeding and treatment. EVIDENCE: Relevant clinical studies and reports published from 1974 to 1994 were examined. A search was conducted of our reprint files, MEDLINE, citations in the articles reviewed and references provided by colleagues. In the MEDLINE search the following terms were used singly or in combination: "hemophilia," "von Willebrand's disease," "Factor VIII," "Factor IX," "von Willebrand factor," "diagnosis," "management," "home care," "comprehensive care," "inhibitor," "AIDS," "hepatitis," "life expectancy," "complications," "practice guidelines," "consensus statement" and "controlled trial." The in-depth review included only articles written in English from North America and Europe that were relevant to human disease and pertinent to a predetermined outline. The availability of treatment products in Canada was also considered. VALUES: Minimizing morbidity and maximizing functional status and quality of life were given a high value. BENEFITS, HARMS AND COSTS: Proper prophylactic or early treatment with appropriate hemostatic agents minimizes morbidity and functional disability and improves quality of life. Economic gains are realized through the reduction of mortality and morbidity and their associated costs. The patient has a better opportunity to contribute to society through gainful employment and the fulfillment of social roles. Potential harms include HIV infection, hepatitis B, hepatitis C and the development of inhibitor antibodies to clotting-factor concentrates. The risk of viral transmission has been minimized through the development of procedures for the viral inactivation of plasma-derived clotting-factor concentrates and through the use of recombinant coagulation-factor concentrates and other non-plasma-derived hemostatic agents. RECOMMENDATIONS: DDAVP is the drug of choice for patients with mild hemophilia or type 1 or 2 (except 2B) von Willebrand's disease whose response to DDAVP in previous testing has been found to be adequate. Therapeutic blood components of choice include recombinant products and virally inactivated plasma-derived products. In Canada the recommended products are recombinant Factor VIII for hemophilia A, high-purity plasma-derived Factor IX for hemophilia B and plasma-derived Factor VIII concentrates containing adequate von Willebrand factor (e.g., Haemate P) for von Willebrand's disease. Dosages vary according to specific indications. Adjunctive antifibrinolytic agents, topical thrombin and fibrin sealant are useful for the treatment of oral or dental bleeds and localized bleeds in accessible sites. In patients with inhibitor antibodies, high-dose human or porcine Factor VIII is usually effective when the inhibitor titre is less than 5 Bethesda units/mL. In nonresponsive patients, or in those whose inhibitor titre is higher, "bypassing" agents (e.g., activated prothrombin-complex concentrate and recombinant Factor VIIa) are useful. Long-term management may include immune-tolerance induction.VALIDATION: These recommendations were reviewed and approved by the Association of Hemophilia Clinic Directors of Canada (AHCDC) and the Medical and Scientific Advisory Committee of the Canadian Hemophilia Society. No similar consensus statements or practice guidelines are available for comparison. SPONSORS: These recommendations were developed at the request of the Canadian Blood Agency, which funds the provision of all coagulation-factor concentrates for people with congenital bleeding disorders, and were developed and endorsed by the AHCDC and the Medical and Scientific Advisory Committee of the Canadian Hemophilia Society. PMID:7600466

Kraft-Wärmekopplung und Blockheiz-Kraftwerke BHKW

NASA Astrophysics Data System (ADS)

Zahoransky, Richard; Allelein, Hans-Josef; Bollin, Elmar; Oehler, Helmut; Schelling, Udo

Die thermischen Wirkungsgrade von Kraftwerken zur Stromerzeugung sind relativ gering. Beispielsweise erreichen moderne Kohlekraftwerke heute bis etwa 45 %, Gasturbinen maximal 40 % und Diesel-Motoren nicht über 50 %. Kombinations-Kraftwerke, Gas- und Dampfturbinen-Prozesse können an die 60 % thermischer Wirkungsgrad bei der Umwandlung der zugeführten Wärme in mechanische bzw. elektrische Energie erzielen. Ein ähnlich hoher Wert wird in Zukunft von den Brennstoffzellen erwartet. Der nicht in Arbeit umgewandelte Anteil der zugeführten Wärme fällt als Abwärme an und geht ungenutzt in die Umgebung. Ein Teil dieser Abwärme lässt sich durch entsprechende Installationen bei allen Kraftwerksprozessen zur Wassererwärmung oder zur Dampferzeugung für industrielle Zwecke nutzen. Für Heizzwecke genügt eine Temperatur der Abwärme von 60 %C bis 80 %C, während die Erzeugung von Industriedampf deutlich höhere Temperaturen voraussetzt.

Systeme mit veränderlicher Teilchenzahl, Gasentartung

NASA Astrophysics Data System (ADS)

Heintze, Joachim

Bisher haben wir die Zustandsgrößen ν (Zahl der Mole) und N (Zahl der Teilchen im System) als konstant betrachtet. In diesem Kapitel wollen wir untersuchen, wie sich Veränderungen von ν bzw. von N beschreiben lassen. Dazu werden wir eine neue thermodynamische Größe einführen, das chemische Potential μ. Als Beispiele für die Veränderung von Teilchenzahlen werden wir diffusive Prozesse und chemische Reaktionen betrachten. Am Ende des Kapitels werden wir die quantenmechanische Gasentartung diskutieren, bei der das chemische Potential ebenfalls eine Rolle spielt. Wir werden feststellen, dass es nicht schwierig ist, einige Eigenschaften dieses interessanten Materiezustands zu verstehen. Wir behandeln das Thema bereits hier und nicht erst in der Quantenphysik am Ende des Buches, weil es in die Wärmelehre gehört und weil auf dieser Grundlage die elektrischen Eigenschaften von Metallen in Bd. III/9 leicht diskutiert werden können.

Clinical and laboratory diagnosis of von Willebrand disease: A synopsis of the 2008 NHLBI/NIH guidelines

PubMed Central

Nichols, William L.; Rick, Margaret E.; Ortel, Thomas L.; Montgomery, Robert R.; Sadler, J. Evan; Yawn, Barbara P.; James, Andra H.; Hultin, Mae B.; Manco-Johnson, Marilyn J.; Weinstein, Mark

2017-01-01

Von Willebrand factor (VWF) mediates blood platelet adhesion and accumulation at sites of blood vessel injury, and also carries coagulation factor VIII (FVIII) that is important for generating procoagulant activity. Von Willebrand disease (VWD), the most common inherited bleeding disorder, affects males and females, and reflects deficiency or defects of VWF that may also cause decreased FVIII. It may also occur less commonly as an acquired disorder (acquired von Willebrand syndrome). This article briefly summarizes selected features of the March 2008 evidence-based clinical and laboratory diagnostic recommendations from the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel for assessment for VWD or other bleeding disorders or risks. Management of VWD is also addressed in the NHLBI guidelines, but is not summarized here. The VWD guidelines are available at the NHLBI Web site (http://www.nhlbi.nih.gov/guidelines/vwd). PMID:19415721

["As we're not willing to hang and behead and not able to deport...". On Emil Kraepelin's influence on Franz von Liszt].

PubMed

Schmidt-Recla, A; Steinberg, H

2008-03-01

Emil Kraepelin started his scientific career with a pamphlet demanding complete restructure of German penal law. It is well known that Kraepelin was a recipient of Cesare Lombroso's theses on degeneration and atavism. Therefore his demand for a correctional law completely replacing penal law is easily understood. Still undiscussed however is the question of whether Kraepelin's brochure had a decisive effect on German criminal law, especially on the so-called Marburg Program of Franz von Liszt, still viewed as the first emergence of modern criminal law and policies in Germany. Examination of this shows that despite major theoretical faults, Kraepelin came to conclusions that correspond remarkably with von Liszt's. Special focus should be directed on the psychologist Wilhelm Wundt, who criticised Kraepelin's juridical attempt in a very kind yet fundamental way, and on the relationship that existed between Kraepelin and von Liszt.

Enhancement of plant metabolite fingerprinting by machine learning.

PubMed

Scott, Ian M; Vermeer, Cornelia P; Liakata, Maria; Corol, Delia I; Ward, Jane L; Lin, Wanchang; Johnson, Helen E; Whitehead, Lynne; Kular, Baldeep; Baker, John M; Walsh, Sean; Dave, Anuja; Larson, Tony R; Graham, Ian A; Wang, Trevor L; King, Ross D; Draper, John; Beale, Michael H

2010-08-01

Metabolite fingerprinting of Arabidopsis (Arabidopsis thaliana) mutants with known or predicted metabolic lesions was performed by (1)H-nuclear magnetic resonance, Fourier transform infrared, and flow injection electrospray-mass spectrometry. Fingerprinting enabled processing of five times more plants than conventional chromatographic profiling and was competitive for discriminating mutants, other than those affected in only low-abundance metabolites. Despite their rapidity and complexity, fingerprints yielded metabolomic insights (e.g. that effects of single lesions were usually not confined to individual pathways). Among fingerprint techniques, (1)H-nuclear magnetic resonance discriminated the most mutant phenotypes from the wild type and Fourier transform infrared discriminated the fewest. To maximize information from fingerprints, data analysis was crucial. One-third of distinctive phenotypes might have been overlooked had data models been confined to principal component analysis score plots. Among several methods tested, machine learning (ML) algorithms, namely support vector machine or random forest (RF) classifiers, were unsurpassed for phenotype discrimination. Support vector machines were often the best performing classifiers, but RFs yielded some particularly informative measures. First, RFs estimated margins between mutant phenotypes, whose relations could then be visualized by Sammon mapping or hierarchical clustering. Second, RFs provided importance scores for the features within fingerprints that discriminated mutants. These scores correlated with analysis of variance F values (as did Kruskal-Wallis tests, true- and false-positive measures, mutual information, and the Relief feature selection algorithm). ML classifiers, as models trained on one data set to predict another, were ideal for focused metabolomic queries, such as the distinctiveness and consistency of mutant phenotypes. Accessible software for use of ML in plant physiology is highlighted.

Detection of bleeding disorders in Lebanon: outcomes of a pilot programme.

PubMed

Djambas Khayat, C; Samaha, H; Noun, P; Bakhos Asmar, J D; Taher, A; Adib, S; Inati, A; Sakr, S

2014-03-01

To promote management and awareness of bleeding disorders in Lebanon, a pilot programme was launched in 2009 by the Lebanese Hemophilia Association assisted by World Federation of Hemophilia. The aim of this study was to diagnose patients with bleeding disorders and to assess the potential challenges in implementing a screening programme. The pilot project was launched in 26 social health centres in the Bekaa valley. The study tools included the evaluation of the Tossetto Bleeding Score and the Pictorial Bleeding Assessment Chart (PBAC) for menstruation. Persons with a bleeding score higher than 2 and PBAC higher than 185 were eligible for further blood tests including the prothrombin time, partial thromboplastin time, complete blood count, bleeding time and von Willebrand ristocetin cofactor activity. 643 patients were enrolled, of whom 60.6% were women. Overall, 91 persons had an abnormal score. 50 eligible patients were tested: 32 had normal tests, nine new patients with severe Von Willebrand were discovered, 4 had VW:RiCo of 40, 3 prolonged APTT and 2 thrombocytopaenia. There was a clear correlation between the severity of the score and the willingness to perform the tests (P = 0.02). Women were reluctant to participate fully when investigators were men. The probability of adherence to the screening protocol is significantly increased when directed by women health care professional. For patients with milder forms, global screening programmes were neither feasible nor acceptable but those more severely affected have to be identified. Providers are crucial in preselecting patients with blood problems who are not coping well. © 2013 John Wiley & Sons Ltd.

Influence of dosing times on cisplatin-induced peripheral neuropathy in rats.

PubMed

Seto, Yoshihiro; Okazaki, Fumiyasu; Horikawa, Keiji; Zhang, Jing; Sasaki, Hitoshi; To, Hideto

2016-09-27

Although cis-diamminedichloro-platinum (CDDP) exhibits strong therapeutic effects in cancer chemotherapy, its adverse effects such as peripheral neuropathy, nephropathy, and vomiting are dose-limiting factors. Previous studies reported that chronotherapy decreased CDDP-induced nephropathy and vomiting. In the present study, we investigated the influence of dosing times on CDDP-induced peripheral neuropathy in rats. CDDP (4 mg/kg) was administered intravenously at 5:00 or 17:00 every 7 days for 4 weeks to male Sprague-Dawley rats, and saline was given to the control group. To assess the dosing time dependency of peripheral neuropathy, von-Frey test and hot-plate test were performed. In order to estimate hypoalgesia, the hot-plate test was performed in rats administered CDDP weekly for 4 weeks. On day 28, the withdrawal latency to thermal stimulation was significantly prolonged in the 17:00-treated group than in the control and 5:00-treated groups. When the von-Frey test was performed to assess mechanical allodynia, the withdrawal threshold was significantly lower in the 5:00 and 17:00-treated groups than in the control group on day 6 after the first CDDP dose. The 5:00-treated group maintained allodynia throughout the experiment with the repeated administration of CDDP, whereas the 17:00-treated group deteriorated from allodynia to hypoalgesia. It was revealed that the severe of CDDP-induced peripheral neuropathy was inhibited in the 5:00-treated group, whereas CDDP-treated groups exhibited mechanical allodynia. These results suggested that the selection of an optimal dosing time ameliorated CDDP-induced peripheral neuropathy.

Characterization of a Putative Spindle Assembly Checkpoint Kinase Mps1, Suggests Its Involvement in Cell Division, Morphogenesis and Oxidative Stress Tolerance in Candida albicans

PubMed Central

Ruhela, Deepa; Kamthan, Ayushi; Maiti, Protiti; Datta, Asis

2014-01-01

In Saccharomyces cerevisiae MPS1 is one of the major protein kinase that governs the spindle checkpoint pathway. The S. cerevisiae structural homolog of opportunistic pathogen Candida albicans CaMPS1, is indispensable for the cell viability. The essentiality of Mps1 was confirmed by Homozygote Trisome test. To determine its biological function in this pathogen conditional mutant was generated through regulatable MET3 promoter. Examination of heterozygous and conditional (+Met/Cys) mps1 mutants revealed a mitosis specific arrest phenotype, where mutants showed large buds with undivided nuclei. Flowcytometry analysis revealed abnormal ploidy levels in mps1mutant. In presence of anti-microtubule drug Nocodazole, mps1 mutant showed a dramatic loss of viability suggesting a role of Mps1 in Spindle Assembly Checkpoint (SAC) activation. These mutants were also defective in microtubule organization. Moreover, heterozygous mutant showed defective in-vitro yeast to hyphae morphological transition. Growth defect in heterozygous mutant suggest haploinsufficiency of this gene. qRT PCR analysis showed around 3 fold upregulation of MPS1 in presence of serum. This expression of MPS1 is dependent on Efg1and is independent of other hyphal regulators like Ras1 and Tpk2. Furthermore, mps1 mutants were also sensitive to oxidative stress. Heterozygous mps1 mutant did not undergo morphological transition and showed 5-Fold reduction in colony forming units in response to macrophage. Thus, the vital checkpoint kinase, Mps1 besides cell division also has a role in morphogenesis and oxidative stress tolerance, in this pathogenic fungus. PMID:25025778

Characterization of a putative spindle assembly checkpoint kinase Mps1, suggests its involvement in cell division, morphogenesis and oxidative stress tolerance in Candida albicans.

PubMed

Kamthan, Mohan; Nalla, Vijaya Kumar; Ruhela, Deepa; Kamthan, Ayushi; Maiti, Protiti; Datta, Asis

2014-01-01

In Saccharomyces cerevisiae MPS1 is one of the major protein kinase that governs the spindle checkpoint pathway. The S. cerevisiae structural homolog of opportunistic pathogen Candida albicans CaMPS1, is indispensable for the cell viability. The essentiality of Mps1 was confirmed by Homozygote Trisome test. To determine its biological function in this pathogen conditional mutant was generated through regulatable MET3 promoter. Examination of heterozygous and conditional (+Met/Cys) mps1 mutants revealed a mitosis specific arrest phenotype, where mutants showed large buds with undivided nuclei. Flowcytometry analysis revealed abnormal ploidy levels in mps1 mutant. In presence of anti-microtubule drug Nocodazole, mps1 mutant showed a dramatic loss of viability suggesting a role of Mps1 in Spindle Assembly Checkpoint (SAC) activation. These mutants were also defective in microtubule organization. Moreover, heterozygous mutant showed defective in-vitro yeast to hyphae morphological transition. Growth defect in heterozygous mutant suggest haploinsufficiency of this gene. qRT PCR analysis showed around 3 fold upregulation of MPS1 in presence of serum. This expression of MPS1 is dependent on Efg1 and is independent of other hyphal regulators like Ras1 and Tpk2. Furthermore, mps1 mutants were also sensitive to oxidative stress. Heterozygous mps1 mutant did not undergo morphological transition and showed 5-Fold reduction in colony forming units in response to macrophage. Thus, the vital checkpoint kinase, Mps1 besides cell division also has a role in morphogenesis and oxidative stress tolerance, in this pathogenic fungus.

Spontaneous Gac Mutants of Pseudomonas Biological Control Strains: Cheaters or Mutualists? ▿

PubMed Central

Driscoll, William W.; Pepper, John W.; Pierson, Leland S.; Pierson, Elizabeth A.

2011-01-01

Bacteria rely on a range of extracellular metabolites to suppress competitors, gain access to resources, and exploit plant or animal hosts. The GacS/GacA two-component regulatory system positively controls the expression of many of these beneficial external products in pseudomonad bacteria. Natural populations often contain variants with defective Gac systems that do not produce most external products. These mutants benefit from a decreased metabolic load but do not appear to displace the wild type in nature. How could natural selection maintain the wild type in the presence of a mutant with enhanced growth? One hypothesis is that Gac mutants are “cheaters” that do not contribute to the public good, favored within groups but selected against between groups, as groups containing more mutants lose access to ecologically important external products. An alternative hypothesis is that Gac mutants have a mutualistic interaction with the wild type, so that each variant benefits by the presence of the other. In the biocontrol bacterium Pseudomonas chlororaphis strain 30-84, Gac mutants do not produce phenazines, which suppress competitor growth and are critical for biofilm formation. Here, we test the predictions of these alternative hypotheses by quantifying interactions between the wild type and the phenazine- and biofilm-deficient Gac mutant within growing biofilms. We find evidence that the wild type and Gac mutants interact mutualistically in the biofilm context, whereas a phenazine-defective structural mutant does not. Our results suggest that the persistence of alternative Gac phenotypes may be due to the stabilizing role of local mutualistic interactions. PMID:21873476

Leishmania infantum HSP70-II null mutant as candidate vaccine against leishmaniasis: a preliminary evaluation.

PubMed

Carrión, Javier; Folgueira, Cristina; Soto, Manuel; Fresno, Manuel; Requena, Jose M

2011-07-27

Visceral leishmaniasis is the most severe form of leishmaniasis and no effective vaccine exists. The use of live attenuated vaccines is emerging as a promising vaccination strategy. In this study, we tested the ability of a Leishmania infantum deletion mutant, lacking both HSP70-II alleles (ΔHSP70-II), to provide protection against Leishmania infection in the L. major-BALB/c infection model. Administration of the mutant line by either intraperitoneal, intravenous or subcutaneous route invariably leads to the production of high levels of NO and the development in mice of type 1 immune responses, as determined by analysis of anti-Leishmania IgG subclasses. In addition, we have shown that ΔHSP70-II would be a safe live vaccine as immunodeficient SCID mice, and hamsters (Mesocricetus auratus), infected with mutant parasites did not develop any sign of pathology. The results suggest that the ΔHSP70-II mutant is a promising and safe vaccine, but further studies in more appropriate animal models (hamsters and dogs) are needed to appraise whether this attenuate mutant would be useful as vaccine against visceral leishmaniasis.

Psychological impact of von Hippel-Lindau genetic screening in patients with a previous history of hemangioblastoma of the central nervous system.

PubMed

Rochette, Claire; Baumstarck, Karine; Canoni-Zattara, Hélène; Abdullah, Ahmad Esmaeel; Figarella-Branger, Dominique; Pertuit, Morgane; Barlier, Anne; Castinetti, Frédéric; Pacak, Karel; Metellus, Philippe; Taïeb, David

2018-05-15

Von Hippel-Lindau (VHL) syndrome is a hereditary cancer syndrome characterized by a high risk of developing benign and malignant tumors, including central nervous system hemangioblastomas (CNS HBs). For an early diagnosis of VHL, before the occurrence of cancers (especially renal cell carcinoma), it is of huge importance to initiate VHL genetic testing in at-risk patients. The aim of the study was to assess the psychological impact of VHL genetic testing in patients previously diagnosed with a CNS HB. From 1999 until 2015, 55 patients underwent surgery for CNS HBs. Eleven patients were already screened for VHL mutations and 3 patients deceased before the start of the study. From the remaining 42 patients, 24 were accepted to be enrolled in the study. Assessment of psychological impact of VHL genetic testing was performed by measuring anxiety levels, mood disorders, quality of life, and psychological consequences of genetic screening. Twenty-one of the enrolled 24 patients underwent VHL genetic testing and 12 patients came back for the communication of positive genetic results. The baseline psychological status did not differ between these 2 groups. Patients who attended the visit of communication of genetic results had similar anxiety levels compared to those who had not. Furthermore, they also experienced an improvement in the level of anxiety and two QoL dimension scores compared to their baseline status. In summary, there is no evidence of a negative psychosocial impact of VHL genetic testing in patients with a previous history of CNS HB. We, therefore, recommend the recall of patients who have not been previously screened.

Genetic screening for von Hippel-Lindau gene mutations in non-syndromic pheochromocytoma: low prevalence and false-positives or misdiagnosis indicate a need for caution.

PubMed

Eisenhofer, G; Vocke, C D; Elkahloun, A; Huynh, T-T; Prodanov, T; Lenders, J W M; Timmers, H J; Benhammou, J N; Linehan, W M; Pacak, K

2012-05-01

Genetic testing of tumor susceptibility genes is now recommended in most patients with pheochromocytoma or paraganglioma (PPGL), even in the absence of a syndromic presentation. Once a mutation is diagnosed there is rarely follow-up validation to assess the possibility of misdiagnosis. This study prospectively examined the prevalence of von Hippel-Lindau (VHL) gene mutations among 182 patients with non-syndromic PPGLs. Follow-up in positive cases included comparisons of biochemical and tumor gene expression data in 64 established VHL patients, with confirmatory genetic testing in cases with an atypical presentation. VHL mutations were detected by certified laboratory testing in 3 of the 182 patients with non-syndromic PPGLs. Two of the 3 had an unusual presentation of diffuse peritoneal metastases and substantial increases in plasma metanephrine, the metabolite of epinephrine. Tumor gene expression profiles in these 2 patients also differed markedly from those associated with established VHL syndrome. One patient was diagnosed with a partial deletion by Southern blot analysis and the other with a splice site mutation. Quantitative polymerase chain reaction, multiplex ligation-dependent probe amplification, and comparative genomic hybridization failed to confirm the partial deletion indicated by certified laboratory testing. Analysis of tumor DNA in the other patient with a splice site alteration indicated no loss of heterozygosity or second hit point mutation. In conclusion, VHL germline mutations represent a minor cause of non-syndromic PPGLs and misdiagnoses can occur. Caution should therefore be exercised in interpreting positive genetic test results as the cause of disease in patients with non-syndromic PPGLs. © Georg Thieme Verlag KG Stuttgart · New York.

Levetiracetam synergises with common analgesics in producing antinociception in a mouse model of painful diabetic neuropathy.

PubMed

Micov, Ana; Tomić, Maja; Pecikoza, Uroš; Ugrešić, Nenad; Stepanović-Petrović, Radica

2015-07-01

Painful diabetic neuropathy is difficult to treat. Single analgesics often have insufficient efficacy and poor tolerability. Combination therapy may therefore be of particular benefit, because it might provide optimal analgesia with fewer adverse effects. This study aimed to examine the type of interaction between levetiracetam, a novel anticonvulsant with analgesic properties, and commonly used analgesics (ibuprofen, aspirin and paracetamol) in a mouse model of painful diabetic neuropathy. Diabetes was induced in C57BL/6 mice with a single high dose of streptozotocin, applied intraperitoneally (150 mg/kg). Thermal (tail-flick test) and mechanical (electronic von Frey test) nociceptive thresholds were measured before and three weeks after diabetes induction. The antinociceptive effects of orally administered levetiracetam, analgesics, and their combinations were examined in diabetic mice that developed thermal/mechanical hypersensitivity. In combination experiments, the drugs were co-administered in fixed-dose fractions of single drug ED50 and the type of interaction was determined by isobolographic analysis. Levetiracetam (10-100 mg/kg), ibuprofen (2-50 mg/kg), aspirin (5-75 mg/kg), paracetamol (5-100 mg/kg), and levetiracetam-analgesic combinations produced significant, dose-dependent antinociceptive effects in diabetic mice in both tests. In the tail-flick test, isobolographic analysis revealed 15-, and 19-fold reduction of doses of both drugs in the combination of levetiracetam with aspirin/ibuprofen, and paracetamol, respectively. In the von Frey test, approximately 7- and 9-fold reduction of doses of both drugs was detected in levetiracetam-ibuprofen and levetiracetam-aspirin/levetiracetam-paracetamol combinations, respectively. These results show synergism between levetiracetam and ibuprofen/aspirin/paracetamol in a model of painful diabetic neuropathy and might provide a useful approach to the treatment of patients suffering from painful diabetic neuropathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Azelainsäure 20 % Creme: Auswirkung auf Lebensqualität und Krankheitsaktivität bei erwachsenen Patientinnen mit Acne vulgaris.

PubMed

Kainz, Julius Thomas; Berghammer, Gabriele; Auer-Grumbach, Piet; Lackner, Verena; Perl-Convalexius, Sylvia; Popa, Rodica; Wolfesberger, Barbara

2016-12-01

Zur Wirksamkeit von Aknetherapien und deren Auswirkungen auf die Lebensqualität erwachsener Patienten liegen kaum Daten vor. ZIEL: Erhebung der Wirkung von Azelainsäure 20 % Creme (Skinoren ® ) auf Akne-Schweregrad und krankheitsbedingte Lebensqualität. Nichtinterventionelle Studie bei erwachsenen Patientinnen mit leichter bis mittelschwerer Akne. Wirksamkeitsparameter waren DLQI sowie Akne-Schweregrad im Gesicht, am Dekolleté sowie am Rücken im Gesamturteil des Prüfarztes (IGA-Skala: Grad 1 = annähernd reine Haut; 2 = leichte Akne; 3 = mittelschwere Akne). Visiten waren zu Studienbeginn sowie nach 4-8 und zwölf Wochen geplant. Von den 251 eingeschlossenen Patientinnen lag zu Studienbeginn bei 59 %, 31 % bzw. 10 % ein IGA-Grad von 1, 2 bzw. 3 vor; die am häufigsten betroffene Hautpartie war das Gesicht (IGA-Grad 2 oder 3: 79 %). Nach zwölf Behandlungswochen war eine signifikante Besserung der Acne vulgaris im Gesicht (IGA-Grad 0 oder 1: 82 %) sowie auf Dekolleté und Rücken feststellbar. Der mediane DLQI-Wert sank von neun zu Studienbeginn auf fünf nach zwölf Behandlungswochen. Neunzig Prozent der behandelnden Ärzte und Patientinnen beurteilten die Verträglichkeit der Behandlung als sehr gut oder gut. Die Anwendung von 20%iger Azelainsäure-Creme führt bei erwachsenen Frauen zu einer signifikanten Besserung der Acne vulgaris und der krankheitsbedingten Lebensqualität. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Sentinel-Lymphknoten-Biopsie des Melanoms mittels Indocyaningrün und "FOVIS"-System.

PubMed

Göppner, Daniela; Nekwasil, Stephan; Jellestad, Anne; Sachse, Alexander; Schönborn, Karl-Heinz; Gollnick, Harald

2017-02-01

Der Nachweis metastatischer Infiltrate im Sentinel-Lymphkoten (SLN) gilt als wesentlicher prognostischer Faktor des Melanoms. Alternativ zur Farbstoffmethode mit Patentblau zum Goldstandard der SLN-Biopsie (SLNB) mittels Radiokolloid wird die fluoreszenzoptische Darstellung mit Hilfe von Indocyaningrün (ICG) und Nahinfrarot (NIR)-Kamerasystem kommuniziert. Im Vergleich zur konventionellen Methode wurde die Wertigkeit des ICG-/NIR-Verfahrens in Abhängigkeit vom Body-Mass-Index (BMI) des Patienten und der Konzentration von ICG bezüglich der Visualisierung des Lymphabstroms und des SLNs untersucht. An zehn Patienten wurde die SLNB mittels Technetium-99m, Patentblau und ICG durchgeführt. Die Fluoreszenz-Darstellung von Lymphbahnen und SLN erfolgte in Echtzeit mittels der NIR-Kameratechnik "FOVIS". Je nach erzielter Bildqualität wurde ICG in einer Dosis von 0,25 mg bis 2,5 mg intrakutan appliziert. Neun der zehn SLN wurden fluoreszenzoptisch identifiziert (90 %), alle zehn radioaktiv (100 %), nur acht (80 %) mittels ICG-Grünfärbung bzw. Patenblau-Markierung. Transdermal wurde ein SLN dargestellt (10 %). In Korrelation zum BMI waren höhere ICG-Mengen, bis zu 2,5 mg intrakutan absolut, in der Darstellung der Lymphbahnen von Vorteil. Die SLN-Fluoreszenzmarkierung mit dem ICG/NIR-Kamera-System "FOVIS" stellt eine sichere Alternative zur Farbstoffmethode mit Patentblau ergänzend zur Radiokolloidmethode mit Technetium-99m dar. Weitere Studien zur optimalen Dosierung von ICG und transdermalen Bildgebung in Relation zum BMI sind notwendig. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Benchmarking care for very low birthweight infants in Ireland and Northern Ireland.

PubMed

Murphy, B P; Armstrong, K; Ryan, C A; Jenkins, J G

2010-01-01

Benchmarking is that process through which best practice is identified and continuous quality improvement pursued through comparison and sharing. The Vermont Oxford Neonatal Network (VON) is the largest international external reference centre for very low birth weight (VLBW) infants. This report from 2004-7 compares survival and morbidity throughout Ireland and benchmarks these results against VON. A standardised VON database for VLBW infants was created in 14 participating centres across Ireland and Northern Ireland. Data on 716 babies were submitted in 2004, increasing to 796 babies in 2007, with centres caring for from 10 to 120 VLBW infants per year. In 2007, mortality rates in VLBW infants varied from 4% to 19%. Standardised mortality ratios indicate that the number of deaths observed was not significantly different from the number expected, based on the characteristics of infants treated. There was no difference in the incidence of severe intraventricular haemorrhage between all-Ireland and VON groups (5% vs 6%, respectively). All-Ireland rates for chronic lung disease (CLD; 15-21%) remained lower than rates seen in the VON group (24-28%). The rates of late onset nosocomial infection in the all-Ireland group (25-26%) remained double those in the VON group (12-13%). This is the first all-Ireland international benchmarking report in any medical specialty. Survival, severe intraventricular haemorrhage and CLD compare favourably with international standards, but rates of nosocomial infection in neonatal units are concerning. Benchmarking clinical outcomes is critical for quality improvement and informing decisions concerning neonatal intensive care service provision.

Eine selbstkonsistente Carleman Linearisierung zur Analyse von Oszillatoren

NASA Astrophysics Data System (ADS)

Weber, Harry; Mathis, Wolfgang

2017-09-01

Die Analyse nichtlinearer dynamischer Schaltungen ist bis heute eine herausfordernde Aufgabe, da nur selten analytische Lösungen angegeben werden können. Daher wurden eine Vielzahl von Methoden entwickelt, um eine qualitative oder quantitative Näherung für die Lösungen der Netzwerkgleichung zu erhalten. Oftmals wird beispielsweise eine Kleinsignalanalyse mit Hilfe einer Taylorreihe in einem Arbeitspunkt durchgeführt, die nach den Gliedern erster Ordnung abgebrochen wird. Allerdings ist diese Linearisierung nur in der Nähe des stabilen Arbeitspunktes für hyperbolische Systeme gültig. Besonders für die Analyse des dynamischen Verhaltens von Oszillatoren treten jedoch nicht-hyperbolische Systeme auf, sodass diese Methode nicht angewendet werden kann Mathis (2000). Carleman hat gezeigt, dass nichtlineare Differentialgleichungen mit polynomiellen Nichtlinearitäten in ein unendliches System von linearen Differentialgleichungen transformiert werden können Carleman (1932). Wird das unendlichdimensionale Gleichungssystem für numerische Zwecke abgebrochen, kann bei Oszillatoren der Übergang in eine stationäre Schwingung (Grenzzyklus) nicht wiedergegeben werden. In diesem Beitrag wird eine selbstkonsistente Carleman Linearisierung zur Untersuchung von Oszillatoren vorgestellt, die auch dann anwendbar ist, wenn die Nichtlinearitäten keinen Polynomen entsprechen. Anstelle einer linearen Näherung um einen Arbeitspunkt, erfolgt mit Hilfe der Carleman Linearisierung eine Approximation auf einem vorgegebenen Gebiet. Da es jedoch mit der selbstkonsistenten Technik nicht möglich ist, das stationäre Verhalten von Oszillatoren zu beschreiben, wird die Berechnung einer Poincaré-Abbildung durchgeführt. Mit dieser ist eine anschließende Analyse des Oszillators möglich.

Hardware-Abbildung eines videobasierten Verfahrens zur echtzeitfähigen Auswertung von Winkelhistogrammen auf eine modulare Coprozessor-Architektur

NASA Astrophysics Data System (ADS)

Flatt, H.; Tarnowsky, A.; Blume, H.; Pirsch, P.

2010-10-01

Dieser Beitrag behandelt die Abbildung eines videobasierten Verfahrens zur echtzeitfähigen Auswertung von Winkelhistogrammen auf eine modulare Coprozessor-Architektur. Die Architektur besteht aus mehreren dedizierten Recheneinheiten zur parallelen Verarbeitung rechenintensiver Bildverarbeitungsverfahren und ist mit einem RISC-Prozessor verbunden. Eine konfigurierbare Architekturerweiterung um eine Recheneinheit zur Auswertung von Winkelhistogrammen von Objekten ermöglicht in Verbindung mit dem RISC eine echtzeitfähige Klassifikation. Je nach Konfiguration sind für die Architekturerweiterung auf einem Xilinx Virtex-5-FPGA zwischen 3300 und 12 000 Lookup-Tables erforderlich. Bei einer Taktfrequenz von 100 MHz können unabhängig von der Bildauflösung pro Einzelbild in einem 25-Hz-Videodatenstrom bis zu 100 Objekte der Größe 256×256 Pixel analysiert werden. This paper presents the mapping of a video-based approach for real-time evaluation of angular histograms on a modular coprocessor architecture. The architecture comprises several dedicated processing elements for parallel processing of computation-intensive image processing tasks and is coupled with a RISC processor. A configurable architecture extension, especially a processing element for evaluating angular histograms of objects in conjunction with a RISC processor, provides a real-time classification. Depending on the configuration of the architecture extension, 3 300 to 12 000 look-up tables are required for a Xilinx Virtex-5 FPGA implementation. Running at a clock frequency of 100 MHz and independently of the image resolution per frame, 100 objects of size 256×256 pixels are analyzed in a 25 Hz video stream by the architecture.

A comparative study of results of the von Langenbeck and the V-Y pushback palatoplasties.

PubMed

Krause, C J; Tharp, R F; Morris, H L

1976-01-01

The incidence of velopharyngeal competence noted in 267 cleft palate patients following palatoplsty has been reviewed. Comparisons have been drawn with regard to the cleft type and the surgical technique performed. Since there were relatively small numbers of subjects in some categories, differences in age at last examination between the von Langenbeck and V-Y palatoplasty groups, some patients were very young at time of evaluation, and a number of different surgeons at different levels of training and experience performed the surgery, the differences in velopharyngeal competence found should be viewed as trends and this report as preliminary. In general, there was a trend toward smaller percentages of patients attaining acceptable velopharyngeal competence as the severity of the cleft increased. Of those with clefts of the soft palate only 86 per cent achieved competence. Among those patients with clefts of the palate only, 67 per cent achieved competence, whereas only 57 per cent of those with clefts of the lip and palate were able to do so. When comparing all cleft types, the V-Y palatoplasty resulted in a significantly higher percentage of velopharyngeal competence (74 per cent) than did the von Langenbeck method (56 per cent), although the data for the V-Y group are probably less reliable than those for the von Langenbeck group. In the soft palate only category, the results were slightly better with the von Langenbeck technique, though not significantly so. In all other cleft types, the results with the V-Y method were better than those with the von Langenbeck.

von Neumann's Law: Theoretical and Microgravity Experimental Comparison for Coarsening Diffusion in Bubble Lattices

NASA Technical Reports Server (NTRS)

Noever, David A.

2000-01-01

The effects of gravity in influencing the theoretical limit for bubble lattice coarsening and aging behavior, otherwise called von Neumann's law, is examined theoretically and experimentally. Preliminary microgravity results will be discussed.

Linking contemporary high resolution magnetic resonance imaging to the von Economo legacy: A study on the comparison of MRI cortical thickness and histological measurements of cortical structure.

PubMed

Scholtens, Lianne H; de Reus, Marcel A; van den Heuvel, Martijn P

2015-08-01

The cerebral cortex is a distinctive part of the mammalian nervous system, displaying a spatial variety in cyto-, chemico-, and myelinoarchitecture. As part of a rich history of histological findings, pioneering anatomists von Economo and Koskinas provided detailed mappings on the cellular structure of the human cortex, reporting on quantitative aspects of cytoarchitecture of cortical areas. Current day investigations into the structure of human cortex have embraced technological advances in Magnetic Resonance Imaging (MRI) to assess macroscale thickness and organization of the cortical mantle in vivo. However, direct comparisons between current day MRI estimates and the quantitative measurements of early anatomists have been limited. Here, we report on a simple, but nevertheless important cross-analysis between the histological reports of von Economo and Koskinas on variation in thickness of the cortical mantle and MRI derived measurements of cortical thickness. We translated the von Economo cortical atlas to a subdivision of the commonly used Desikan-Killiany atlas (as part of the FreeSurfer Software package and a commonly used parcellation atlas in studies examining MRI cortical thickness). Next, values of "width of the cortical mantle" as provided by the measurements of von Economo and Koskinas were correlated to cortical thickness measurements derived from high-resolution anatomical MRI T1 data of 200+ subjects of the Human Connectome Project (HCP). Cross-correlation revealed a significant association between group-averaged MRI measurements of cortical thickness and histological recordings (r = 0.54, P < 0.001). Further validating such a correlation, we manually segmented the von Economo parcellation atlas on the standardized Colin27 brain dataset and applied the obtained three-dimensional von Economo segmentation atlas to the T1 data of each of the HCP subjects. Highly consistent with our findings for the mapping to the Desikan-Killiany regions, cross-correlation between in vivo MRI cortical thickness and von Economo histology-derived values of cortical mantle width revealed a strong positive association (r = 0.62, P < 0.001). Linking today's state-of-the-art T1-weighted imaging to early histological examinations our findings indicate that MRI technology is a valid method for in vivo assessment of thickness of human cortex. © 2015 Wiley Periodicals, Inc.

Reduced alcohol consumption in mice lacking preprodynorphin.

PubMed Central

Blednov, Yuri A.; Walker, Danielle; Martinez, Marni; Harris., R. Adron

2007-01-01

Many studies suggest a role for endogenous opioid peptides and their receptors in regulation of ethanol intake. It is commonly accepted that the κ-opioid receptors and their endogenous ligands, dynorphins, produce a dysphoric state and therefore may be responsible for avoidance of alcohol. We used mutant mice lacking preprodynorphin in a variety of behavioral tests of alcohol actions. Null mutant female, but not male, mice showed significantly lower preference for alcohol and consumed lower amounts of alcohol in a two-bottle choice test as compared with wild-type littermates. In the same test, knockout mice of both sexes showed a strong reduction of preference for saccharin compared to control mice. In contrast, under conditions of limited (4 hours) access (light phase of the light/dark cycle), null mutant mice did not show any differences in consumption of saccharin but they showed significantly reduced intake of sucrose. To determine the possible cause for reduction of ethanol preference and intake, we studied other ethanol-related behaviors in mice lacking the preprodynorphin gene. There were no differences between null mutant and wild type mice in ethanol-induced loss of righting reflex, acute ethanol withdrawal, ethanol-induced conditioned place preference or conditioned taste aversion to ethanol. These results indicate that deletion of preprodynorphin leads to substantial reduction of alcohol intake in female mice, and suggest thath this is caused by decreased orosensory reward of alcohol (sweet taste and/or palatability). PMID:17307643

Reduced alcohol consumption in mice lacking preprodynorphin.

PubMed

Blednov, Yuri A; Walker, Danielle; Martinez, Marni; Harris, R Adron

2006-10-01

Many studies suggest a role for endogenous opioid peptides and their receptors in regulation of ethanol intake. It is commonly accepted that the kappa-opioid receptors and their endogenous ligands, dynorphins, produce a dysphoric state and therefore may be responsible for avoidance of alcohol. We used mutant mice lacking preprodynorphin in a variety of behavioral tests of alcohol actions. Null mutant female, but not male, mice showed significantly lower preference for alcohol and consumed lower amounts of alcohol in a two-bottle choice test as compared with wild-type littermates. In the same test, knockout mice of both sexes showed a strong reduction of preference for saccharin compared to control mice. In contrast, under conditions of limited (4 h) access (light phase of the light/dark cycle), null mutant mice did not show any differences in consumption of saccharin, but they showed significantly reduced intake of sucrose. To determine the possible cause for reduction of ethanol preference and intake, we studied other ethanol-related behaviors in mice lacking the preprodynorphin gene. There were no differences between null mutant and wild-type mice in ethanol-induced loss of righting reflex, acute ethanol withdrawal, ethanol-induced conditioned place preference, or conditioned taste aversion to ethanol. These results indicate that deletion of preprodynorphin leads to substantial reduction of alcohol intake in female mice, and suggest that this is caused by decreased orosensory reward of alcohol (sweet taste and/or palatability).

Caspofungin Treatment of Aspergillus fumigatus Results in ChsG-Dependent Upregulation of Chitin Synthesis and the Formation of Chitin-Rich Microcolonies

PubMed Central

Walker, Louise A.; Lee, Keunsook K.; Munro, Carol A.

2015-01-01

Treatment of Aspergillus fumigatus with echinocandins such as caspofungin inhibits the synthesis of cell wall β-1,3-glucan, which triggers a compensatory stimulation of chitin synthesis. Activation of chitin synthesis can occur in response to sub-MICs of caspofungin and to CaCl2 and calcofluor white (CFW), agonists of the protein kinase C (PKC), and Ca2+-calcineurin signaling pathways. A. fumigatus mutants with the chs gene (encoding chitin synthase) deleted (ΔAfchs) were tested for their response to these agonists to determine the chitin synthase enzymes that were required for the compensatory upregulation of chitin synthesis. Only the ΔAfchsG mutant was hypersensitive to caspofungin, and all other ΔAfchs mutants tested remained capable of increasing their chitin content in response to treatment with CaCl2 and CFW and caspofungin. The resulting increase in cell wall chitin content correlated with reduced susceptibility to caspofungin in the wild type and all ΔAfchs mutants tested, with the exception of the ΔAfchsG mutant, which remained sensitive to caspofungin. In vitro exposure to the chitin synthase inhibitor, nikkomycin Z, along with caspofungin demonstrated synergistic efficacy that was again AfChsG dependent. Dynamic imaging using microfluidic perfusion chambers demonstrated that treatment with sub-MIC caspofungin resulted initially in hyphal tip lysis. However, thickened hyphae emerged that formed aberrant microcolonies in the continued presence of caspofungin. In addition, intrahyphal hyphae were formed in response to echinocandin treatment. These in vitro data demonstrate that A. fumigatus has the potential to survive echinocandin treatment in vivo by AfChsG-dependent upregulation of chitin synthesis. Chitin-rich cells may, therefore, persist in human tissues and act as the focus for breakthrough infections. PMID:26169407

Chemical Genomic Screening of a Saccharomyces cerevisiae Genomewide Mutant Collection Reveals Genes Required for Defense against Four Antimicrobial Peptides Derived from Proteins Found in Human Saliva

PubMed Central

Bhatt, Sanjay; Schoenly, Nathan E.; Lee, Anna Y.; Nislow, Corey; Bobek, Libuse A.

2013-01-01

To compare the effects of four antimicrobial peptides (MUC7 12-mer, histatin 12-mer, cathelicidin KR20, and a peptide containing lactoferricin amino acids 1 to 11) on the yeast Saccharomyces cerevisiae, we employed a genomewide fitness screen of combined collections of mutants with homozygous deletions of nonessential genes and heterozygous deletions of essential genes. When an arbitrary fitness score cutoffs of 1 (indicating a fitness defect, or hypersensitivity) and −1 (indicating a fitness gain, or resistance) was used, 425 of the 5,902 mutants tested exhibited altered fitness when treated with at least one peptide. Functional analysis of the 425 strains revealed enrichment among the identified deletions in gene groups associated with the Gene Ontology (GO) terms “ribosomal subunit,” “ribosome biogenesis,” “protein glycosylation,” “vacuolar transport,” “Golgi vesicle transport,” “negative regulation of transcription,” and others. Fitness profiles of all four tested peptides were highly similar, particularly among mutant strains exhibiting the greatest fitness defects. The latter group included deletions in several genes involved in induction of the RIM101 signaling pathway, including several components of the ESCRT sorting machinery. The RIM101 signaling regulates response of yeasts to alkaline and neutral pH and high salts, and our data indicate that this pathway also plays a prominent role in regulating protective measures against all four tested peptides. In summary, the results of the chemical genomic screens of S. cerevisiae mutant collection suggest that the four antimicrobial peptides, despite their differences in structure and physical properties, share many interactions with S. cerevisiae cells and consequently a high degree of similarity between their modes of action. PMID:23208710

[The quantitative testing of V617F mutation in gen JAK2 using pyrosequencing technique].

PubMed

Dunaeva, E A; Mironov, K O; Dribnokhodova, T E; Subbotina, E E; Bashmakova; Ol'hovskiĭ, I A; Shipulin, G A

2014-11-01

The somatic mutation V617F in gen JAK2 is a frequent cause of chronic myeloprolific diseases not conditioned by BCR/ABL mutation. The quantitative testing of relative percentage of mutant allele can be used in establishing severity of disease and its prognosis and in prescription of remedy inhibiting activity of JAK2. To quantitatively test mutation the pyrosequencing technique was applied. The developed technique permits detecting and quantitatively, testing percentage of mutation fraction since 7%. The "gray zone" is presented by samples with percentage of mutant allele from 4% to 7%. The dependence of expected percentage of mutant fraction in analyzed sample from observed value of signal is described by equation of line with regression coefficients y = - 0.97, x = -1.32 and at that measurement uncertainty consists ± 0.7. The developed technique is approved officially on clinical material from 192 patients with main forms of myeloprolific diseases not conditioned by BCR/ABL mutation. It was detected 64 samples with mautant fraction percentage from 13% to 91%. The developed technique permits implementing monitoring of therapy of myeloprolific diseases and facilitates to optimize tactics of treatment.

Mutant prevention concentrations of four carbapenems against gram-negative rods.

PubMed

Credito, Kim; Kosowska-Shick, Klaudia; Appelbaum, Peter C

2010-06-01

We tested the propensities of four carbapenems to select for resistant Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii mutants by determining the mutant prevention concentrations (MPCs) for 100 clinical strains with various ss-lactam phenotypes. Among the members of the Enterobacteriaceae family and A. baumannii strains, the MPC/MIC ratios were mostly 2 to 4. In contrast, for P. aeruginosa the MPC/MIC ratios were 4 to > or =16. The MPC/MIC ratios for beta-lactamase-positive K. pneumoniae and E. coli isolates were much higher (range, 4 to >16 microg/ml) than those for ss-lactamase-negative strains.

Mutagenizing brewing yeast strain for improving fermentation property of beer.

PubMed

Liu, Zengran; Zhang, Guangyi; Sun, Yunping

2008-07-01

A brewing yeast mutant with perfect sugar fermentation capacity was isolated by mutagenizing the Saccharomyces pastorianus transformant, which carries an integrated glucoamylase gene and has one copy of non-functional alpha-acetolactate synthase gene. The mutant was able to utilize maltotriose efficiently, and the maltotriose fermentability in YNB-2% maltotriose medium increased from 32.4% to 72.0% after 5 d in shaking culture. The wort fermentation test confirmed that the sugar fermentation property of the mutant was greatly improved, while its brewing performances were analogous to that of the wild-type strain and the characteristic trait of shortened beer maturation period was retained. Therefore, we believe that the brewing yeast mutant would benefit the beer industry and would be useful for low caloric beer production.

Schwann cell hyperplasia and tumors in transgenic mice expressing a naturally occurring mutant NF2 protein

PubMed Central

Giovannini, Marco; Robanus-Maandag, Els; Niwa-Kawakita, Michiko; van der Valk, Martin; Woodruff, James M.; Goutebroze, Laurence; Mérel, Philippe; Berns, Anton; Thomas, Gilles

1999-01-01

Specific mutations in some tumor suppressor genes such as p53 can act in a dominant fashion. We tested whether this mechanism may also apply for the neurofibromatosis type-2 gene (NF2) which, when mutated, leads to schwannoma development. Transgenic mice were generated that express, in Schwann cells, mutant NF2 proteins prototypic of natural mutants observed in humans. Mice expressing a NF2 protein with an interstitial deletion in the amino-terminal domain showed high prevalence of Schwann cell-derived tumors and Schwann cell hyperplasia, whereas those expressing a carboxy-terminally truncated protein were normal. Our results indicate that a subset of mutant NF2 alleles observed in patients may encode products with dominant properties when overexpressed in specific cell lineages. PMID:10215625

p.Arg82Leu von Hippel-Lindau (VHL) Gene Mutation among Three Members of a Family with Familial Bilateral Pheochromocytoma in India: Molecular Analysis and In Silico Characterization

PubMed Central

John, Anulekha Mary; C, George Priya Doss; Ebenazer, Andrew; Seshadri, Mandalam Subramaniam; Nair, Aravindan; Rajaratnam, Simon; Pai, Rekha

2013-01-01

Various missense mutations in the VHL gene have been reported among patients with familial bilateral pheochromocytoma. However, the p.Arg82Leu mutation in the VHL gene described here among patients with familial bilateral pheochromocytoma, has never been reported previously in a germline configuration. Interestingly, long-term follow-up of these patients indicated that the mutation might have had little impact on the normal function of the VHL gene, since all of them have remained asymptomatic. We further attempted to correlate this information with the results obtained by in silico analysis of this mutation using SIFT, PhD-SNP SVM profile, MutPred, PolyPhen2, and SNPs&GO prediction tools. To gain, new mechanistic insight into the structural effect, we mapped the mutation on to 3D structure (PDB ID 1LM8). Further, we analyzed the structural level changes in time scale level with respect to native and mutant protein complexes by using 12 ns molecular dynamics simulation method. Though these methods predict the mutation to have a pathogenic potential, it remains to be seen if these patients will eventually develop symptomatic disease. PMID:23626751

Director von Braun Presents General Medaris With Golf Bag

NASA Technical Reports Server (NTRS)

1959-01-01

Marshall Space Flight Center Director Wernher von Braun presents General J.B. Medaris with a new golf bag. General Medaris, (left) was a Commander of the Army Ballistic Missile Agency (ABMA) in Redstone Arsenal, Alabama during 1955 to 1958.

Alexander von Humboldt and the Origins of Landscape Archaeology.

ERIC Educational Resources Information Center

Mathewson, Kent

1986-01-01

Reviews the life, theories, and influence of Alexander von Humboldt, the early nineteenth century founder of modern geography. Maintains that Humboldt's novel approaches to the study of landscape antiquities have value for contemporary students in cultural and historical geography. (JDH)

Mittelwert- und Arbeitstaktsynchrone Simulation von Dieselmotoren

NASA Astrophysics Data System (ADS)

Zahn, Sebastian

Getrieben durch die immer restriktiveren Anforderungen an das Emissions- und Verbrauchsverhalten moderner Verbrennungsmotoren steigt die Komplexität von Motormanagementsystemen mit jeder Modellgeneration an. Damit geht nicht nur eine Zunahme des Softwareumfangs von Steuergeräten sondern zugleich ein deutlicher Anstieg des Applikations-, Vermessungs- und Testaufwandes einher. Zur Effizienzsteigerung des Software- und Funktionsentwicklungsprozesses haben sich daher in der Automobilindustrie sowie in Forschungsinstituten verschiedene modell- und simulationsbasierte Methoden wie die Model-in-the-Loop (MiL) Simulation, die Software-in-the-Loop (SiL) Simulation, das Rapid Control Prototyping (RCP) sowie die Hardware-in-the-Loop (HiL) Simulation etabliert.

Planungsunterstützung für Pankreasoperationen bei Hyperinsulinismus von Kindern

NASA Astrophysics Data System (ADS)

Dornheim, J.; Preim, B.; Preim, U.; Mohnike, K.; Blankenstein, O.; Füchtner, F.; Mohnike, W.; Empting, S.; Mohnike, K.

Auf Basis von sechs PET/CT-Datensätzen des Pankreas wird eine Computerunterstützung für die Teilresektion der Bauchspeicheldr üse (Pankreas) bei fokalem Hyperinsulinismus von Kindern entwickelt. Ziel ist es, die Lokalisation des krankhaften Fokus im Pankreasgewebe präoperativ dreidimensional zu visualisieren, um so die Sicherheit des Eingriffs zu erhöhen. Die relevanten anatomischen Strukturen werden im CT segmentiert und anschließend dreidimensional visualisiert. Der im PET erkennbare Fokus wird in diese anatomische 3D-Visualisierung eingeblendet. Es zeigt sich eine klare Erkennbarkeit des Fokus in allen sechs Fällen.

Visualisierung analoger Schaltungen durch 3-D Animation von transienten SPICE-Simulationen

NASA Astrophysics Data System (ADS)

Becker, J.; Manoli, Y.

2007-06-01

Für das Zeichnen analoger Schaltpläne wird oft versucht, die Potentialverteilung in der entsprechenden Schaltung auszunutzen, um eine Platzierung der Bauteile nach abfallendem Potential vorzunehmen. Mit Hilfe von Computerunterstützung gelingt es, eine verallgemeinerte dreidimensionale Platzierungsstrategie anzuwenden, die allein auf Grund der Potentialwerte einer Schaltung die automatische Generierung einer technisch exakten Potentialdarstellung erlaubt. Somit ist es möglich, die Ergebnisse von transienten SPICE-Simulationen in jedem Zeitschritt darzustellen und eine Animation des zeitlichen Verhaltens zu erzeugen. Die Umsetzung dieser Methode zur Einbettung in eine webbasierte Lern - und Arbeitsplattform wird im Folgenden erläutert.

The smooth entropy formalism for von Neumann algebras

NASA Astrophysics Data System (ADS)

Berta, Mario; Furrer, Fabian; Scholz, Volkher B.

2016-01-01

We discuss information-theoretic concepts on infinite-dimensional quantum systems. In particular, we lift the smooth entropy formalism as introduced by Renner and collaborators for finite-dimensional systems to von Neumann algebras. For the smooth conditional min- and max-entropy, we recover similar characterizing properties and information-theoretic operational interpretations as in the finite-dimensional case. We generalize the entropic uncertainty relation with quantum side information of Tomamichel and Renner and discuss applications to quantum cryptography. In particular, we prove the possibility to perform privacy amplification and classical data compression with quantum side information modeled by a von Neumann algebra.

"The captain and canon" C. W. A. von Wahl (1760-1846) (German Title: "Der Hauptmann und Kanonikus" C. W. A. von Wahl (1760-1846) )

NASA Astrophysics Data System (ADS)

Brosche, Peter

Von Wahl was an active member of the group of independent scholars, who were working in the German states within Goethe's time, and who performed astrometric and geodetic observations and calculations. Here we present some cornerstones of his life; longer intervals of it took place in Allstedt south of the Harz and in Halberstadt. Small scientific assets have been preserved at the Universitäts-Sternwarte Bonn. Therein, a lecture on secular variations of the ecliptic is of singular nature.

Transporterscheinungen

NASA Astrophysics Data System (ADS)

Heintze, Joachim

In diesem Kapitel werden wir uns vornehmlich mit zwei Vorgängen befassen, ohne die das Erreichen des thermischen Gleichgewichts und die Veränderung des thermischen Zustands eines Systems unmöglich wäre: Wärmeleitung und Diffusion. Bei der Wärmeleitung wird die kinetische Energie der Teilchen durch Stöße auf die Nachbarn übertragen: Es handelt sich um den Transport von Wärmeenergie. Unter Diffusion versteht man den Transport von Molekülen aufgrund ihrer Wärmebewegung. Sie tritt in Erscheinung, wenn in einem System verschiedene Arten von Molekülen vorhanden und ungleichmäßig verteilt sind.

The smooth entropy formalism for von Neumann algebras

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berta, Mario, E-mail: berta@caltech.edu; Furrer, Fabian, E-mail: furrer@eve.phys.s.u-tokyo.ac.jp; Scholz, Volkher B., E-mail: scholz@phys.ethz.ch

2016-01-15

We discuss information-theoretic concepts on infinite-dimensional quantum systems. In particular, we lift the smooth entropy formalism as introduced by Renner and collaborators for finite-dimensional systems to von Neumann algebras. For the smooth conditional min- and max-entropy, we recover similar characterizing properties and information-theoretic operational interpretations as in the finite-dimensional case. We generalize the entropic uncertainty relation with quantum side information of Tomamichel and Renner and discuss applications to quantum cryptography. In particular, we prove the possibility to perform privacy amplification and classical data compression with quantum side information modeled by a von Neumann algebra.

Universal Local Symmetries and Nonsuperposition in Classical Mechanics

NASA Astrophysics Data System (ADS)

Gozzi, Ennio; Pagani, Carlo

2010-10-01

In the Hilbert space formulation of classical mechanics, pioneered by Koopman and von Neumann, there are potentially more observables than in the standard approach to classical mechanics. In this Letter, we show that actually many of those extra observables are not invariant under a set of universal local symmetries which appear once the Koopman and von Neumann formulation is extended to include the evolution of differential forms. Because of their noninvariance, those extra observables have to be removed. This removal makes the superposition of states in the Koopman and von Neumann formulation, and as a consequence also in classical mechanics, impossible.

Finite element analysis of stress distribution on the mandible and condylar fracture osteosynthesis during various clenching tasks.

PubMed

Hijazi, Loai; Hejazi, Wael; Darwich, Mhd Ayham; Darwich, Khaldoun

2016-12-01

The purpose of the study was to evaluate the effect of clenching tasks on the stress and strain of condylar osteosynthesis screws and plates, as well as on the stress, strain distribution and displacement on the whole mandible and bone surrounding screws. Three-dimensional finite element models of the mandible, two straight four-hole plates and eight screws were established. Six static clenching tasks were simulated in this study: incisal clench (INC), intercuspal position (ICP), right unilateral molar clench (RMOL), left unilateral molar clench (LMOL), right group function (RGF) and left group function (LGF). Based on the simulation of the six clenching tasks, none of the inserted screws and plates were broken or bended. For the whole mandibular bone, the maximum von Mises stress and von Mises strain observed were yielded by the ICP. For the bone surrounding the inserted screws, the maximum von Mises stress and von Mises strain were yielded by the LMOL (49.2 MPa and 3795.1 μ). Clenching tasks had significant effects on the stress distribution on the condylar osteosynthesis and the bone surrounding screws. Contralateral occlusion task (LMOL) had the maximal results of von Mises stress and strain and healing problems could be occur, this result confirms the importance of soft diet after surgery.

Biokompatible Metalle

NASA Astrophysics Data System (ADS)

Ha, Suk-Woo; Wintermantel, Erich

Metalle als Implantatwerkstoffe werden in der Medizin für zwei Hauptanwendungen eingesetzt: für Prothesen des totalen Gelenkersatzes wie beispielsweise Hüft-, Knie- und Schulterprothesen und für Fixationselemente zur Stabilisierung von Frakturen. Beispiele hierfür sind Osteosyntheseplatten, Marknägel, Schrauben, Drähte und Stents. Eine der ersten Anwendungen von Metallen im menschlichen Körper war die Fixation von Fragmenten eines gebrochenen Humerus (Oberarmknochen) mit einem Metalldraht durch zwei französische Physiker im Jahr 1775 [1]. Ausführliche Untersuchungen zur Verträglichkeit von Metallen im menschlichen Körper wurden bereits im frühen 19. Jahrhundert durchgeführt. Von den untersuchten Werkstoffen verursachten die edlen Metalle wie Gold, Silber und Platin aufgrund ihrer Korrosionsbeständigkeit und Körperverträglichkeit die geringsten Reizungen im menschlichen Körper. Die klinische Anwendung der Edelmetalle war jedoch wegen der geringen mechanischen Eigenschaften beschränkt. Andere Metalle wie Messing, Kupfer oder Eisen wiesen vergleichsweise höhere Festigkeitswerte auf, sie waren jedoch aufgrund der geringen Korrosionsbeständigkeit und Biokompatibilität nicht für den klinischen Einsatz geeignet. Ein weiteres Problem stellte die Gefahr der Infektion durch unsterile Instrumente und Implantate dar. Gegen Ende des 19. Jahrhunderts hielt die antiseptische Operationsmethode Einzug in die Kliniken, die z. B. erfolgreiche Operationen mit Silberdraht ermöglichte.

Finite element analysis of a bone healing model: 1-year follow-up after internal fixation surgery for femoral fracture.

PubMed

Jiang-Jun, Zhou; Min, Zhao; Ya-Bo, Yan; Wei, Lei; Ren-Fa, Lv; Zhi-Yu, Zhu; Rong-Jian, Chen; Wei-Tao, Yu; Cheng-Fei, Du

2014-03-01

Finite element analysis was used to compare preoperative and postoperative stress distribution of a bone healing model of femur fracture, to identify whether broken ends of fractured bone would break or not after fixation dislodgement one year after intramedullary nailing. Method s: Using fast, personalized imaging, bone healing models of femur fracture were constructed based on data from multi-slice spiral computed tomography using Mimics, Geomagic Studio, and Abaqus software packages. The intramedullary pin was removed by Boolean operations before fixation was dislodged. Loads were applied on each model to simulate a person standing on one leg. The von Mises stress distribution, maximum stress, and its location was observed. Results : According to 10 kinds of display groups based on material assignment, the nodes of maximum and minimum von Mises stress were the same before and after dislodgement, and all nodes of maximum von Mises stress were outside the fracture line. The maximum von Mises stress node was situated at the bottom quarter of the femur. The von Mises stress distribution was identical before and after surgery. Conclusion : Fast, personalized model establishment can simulate fixation dislodgement before operation, and personalized finite element analysis was performed to successfully predict whether nail dislodgement would disrupt femur fracture or not.

Holding-time-aware asymmetric spectrum allocation in virtual optical networks

NASA Astrophysics Data System (ADS)

Lyu, Chunjian; Li, Hui; Liu, Yuze; Ji, Yuefeng

2017-10-01

Virtual optical networks (VONs) have been considered as a promising solution to support current high-capacity dynamic traffic and achieve rapid applications deployment. Since most of the network services (e.g., high-definition video service, cloud computing, distributed storage) in VONs are provisioned by dedicated data centers, needing different amount of bandwidth resources in both directions, the network traffic is mostly asymmetric. The common strategy, symmetric provisioning of traffic in optical networks, leads to a waste of spectrum resources in such traffic patterns. In this paper, we design a holding-time-aware asymmetric spectrum allocation module based on SDON architecture and an asymmetric spectrum allocation algorithm based on the module is proposed. For the purpose of reducing spectrum resources' waste, the algorithm attempts to reallocate the idle unidirectional spectrum slots in VONs, which are generated due to the asymmetry of services' bidirectional bandwidth. This part of resources can be exploited by other requests, such as short-time non-VON requests. We also introduce a two-dimensional asymmetric resource model for maintaining idle spectrum resources information of VON in spectrum and time domains. Moreover, a simulation is designed to evaluate the performance of the proposed algorithm, and results show that our proposed asymmetric spectrum allocation algorithm can improve the resource waste and reduce blocking probability.

Identifikationsverfahren zur Analyse von EEG-Signalen bei Epilepsie mit Reaktions-Diffusions Netzwerken

NASA Astrophysics Data System (ADS)

Gollas, F.; Tetzlaff, R.

2007-06-01

Partielle Differentialgleichungen des Reaktions-Diffusions-Typs beschreiben Phänomene wie Musterbildung, nichtlineare Wellenausbreitung und deterministisches Chaos und werden oft zur Untersuchung komplexer Vorgänge auf den Gebieten der Biologie, Chemie und Physik herangezogen. Zellulare Nichtlineare Netzwerke (CNN) sind eine räumliche Anordnung vergleichsweise einfacher dynamischer Systeme, die eine lokale Kopplung untereinander aufweisen. Durch eine Diskretisierung der Ortsvariablen können Reaktions-Diffusions-Gleichungen häufig auf CNN mit nichtlinearen Gewichtsfunktionen abgebildet werden. Die resultierenden Reaktions-Diffusions-CNN (RD-CNN) weisen dann in ihrer Dynamik näherungsweise gleiches Verhalten wie die zugrunde gelegten Reaktions-Diffusions-Systeme auf. Werden RD-CNN zur Identifikation neuronaler Strukturen anhand von EEG-Signalen herangezogen, so besteht die Möglichkeit festzustellen, ob das gefundene Netzwerk lokale Aktivität aufweist. Die von Chua eingeführte Theorie der lokalen Aktivität Chua (1998); Dogaru und Chua (1998) liefert eine notwendige Bedingung für das Auftreten von emergentem Verhalten in zellularen Netzwerken. Änderungen in den Parametern bestimmter RD-CNN könnten auf bevorstehende epileptische Anfälle hinweisen. In diesem Beitrag steht die Identifikation neuronaler Strukturen anhand von EEG-Signalen durch Reaktions-Diffusions-Netzwerke im Vordergrund der dargestellten Untersuchungen. In der Ergebnisdiskussion wird insbesondere auch die Frage nach einer geeigneten Netzwerkstruktur mit minimaler Komplexität behandelt.

Influence of stationary and non-stationary conditions on drying time and mechanical properties of a porcelain slab

NASA Astrophysics Data System (ADS)

Hammouda, Imen; Mihoubi, Daoued

2017-12-01

This work deals with a numerical study of the response of a porcelain slab when subjected to convective drying in stationary and non-stationary conditions. The used model describes heat, mass, and momentum transfers is applied to an unsaturated viscoelastic medium described by a Maxwell model. The numerical code allows us to determine the effect of the surrounding air temperature on drying kinetics and on mechanical stress intensities. Von Mises stresses are analysed in order to foresee an eventual damage that may occur during drying. Simulation results for several temperatures in the range of [30 °C, 90 °C] shows that for the temperature from 30 °C to 60 °C, Von Mises stresses are always lower than the yield strength. But above 70 °C, Von Mises stresses are higher than the ultimate strength, and consequently there is a risk of crack at the end of the constant drying rate period. The idea proposed in this work is to integrate a reducing temperature phase when the predicted Von Mises stress intensity exceeds the admissible stress. Simulation results shows that a non-stationary convective drying (90-60 °C) allows us to optimize costs and quality by reducing the drying time and maintaining Von Mises stress values under the admissible stress.

Evaluation of vaccine candidate potential of deltaaroA, deltahtrA and deltaaroAdeltahtrA mutants of Salmonella enterica subspecies enterica serovar Abortusequi in guinea pigs.

PubMed

Singh, Bhoj Raj; Chandra, Mudit; Hansda, Dhananjoy; Alam, Javed; Babu, Narayanan; Siddiqui, Mehtab Z; Agrawal, Ravi K; Sharma, Gautam

2013-04-01

Salmonella enterica subspecies enterica serovar Abortusequi (S. Abortusequi), a host adapted Salmonella causes abortions, still births and foal mortality in equids. Though known since more than 100 years, it is still a problem in many of the developing countries including India. There is dearth of really good vaccine affording immunity lasting at least for one full gestation. In search of a potential vaccine candidate, three defined deletion mutants (deltaaroA, deltahtrA and deltaaroAdeltahtrA) of S. Abortusequi were tested in guinea pig model for attenuation, safety, immunogenicity, humoral immune response, protective efficacy and persistence in host. The deltahtrA and deltaaroAdeltahtrA mutants were found to be safe on oral inoculation in doses as high as 4.2 x 10(9) cfu/animal. Also through subcutaneous inoculation deltaaroAdeltahtrA mutant did not induce any abortion in pregnant guinea pigs. All the three mutants did not induce any illness or death in 1-2 week-old baby guinea pigs except deltahtrA mutant which caused mortality on intraperitoneal inoculation. Inoculation with mutants protected against challenge and increased breeding efficiency of guinea pigs. After >4.5 months of mutant inoculation, guinea pigs were protected against abortifacient dose of wild type S. Abortusequi and mother guinea pigs also conferred resistance to their babies to the similar challenge. Early humoral immune response of S. Abortusequi mutants was characteristic. Faecal excretion of deltaaroA and htrA mutants was detected up to 45 days of inoculation in guinea pigs while deltaaroAdeltahtrA mutant could not be detected after 21 days of inoculation. The results indicated that the double deletion mutant (deltaaroAdeltahtrA) was the most effective and safe candidate for vaccination against S. Abortusequi through mucosal route of inoculation.

Proteomic analysis of the flooding tolerance mechanism in mutant soybean.

PubMed

Komatsu, Setsuko; Nanjo, Yohei; Nishimura, Minoru

2013-02-21

Flooding stress of soybean is a serious problem because it reduces growth; however, flooding-tolerant cultivars have not been identified. To analyze the flooding tolerance mechanism of soybean, the flooding-tolerant mutant was isolated and analyzed using a proteomic technique. Flooding-tolerance tests were repeated five times using gamma-ray irradiated soybeans, whose root growth (M6 stage) was not suppressed even under flooding stress. Two-day-old wild-type and mutant plants were subjected to flooding stress for 2days, and proteins were identified using a gel-based proteomic technique. In wild-type under flooding stress, levels of proteins related to development, protein synthesis/degradation, secondary metabolism, and the cell wall changed; however, these proteins did not markedly differ in the mutant. In contrast, an increased number of fermentation-related proteins were identified in the mutant under flooding stress. The root tips of mutant plants were not affected by flooding stress, even though the wild-type plants had damaged root. Alcohol dehydrogenase activity in the mutant increased at an early stage of flooding stress compared with that of the wild-type. Taken together, these results suggest that activation of the fermentation system in the early stages of flooding may be an important factor for the acquisition of flooding tolerance in soybean. Copyright © 2012 Elsevier B.V. All rights reserved.

Diffusible signal factor-repressed extracellular traits enable attachment of Xylella fastidiosa to insect vectors and transmission.

PubMed

Baccari, Clelia; Killiny, Nabil; Ionescu, Michael; Almeida, Rodrigo P P; Lindow, Steven E

2014-01-01

The hypothesis that a wild-type strain of Xylella fastidiosa would restore the ability of rpfF mutants blocked in diffusible signal factor production to be transmitted to new grape plants by the sharpshooter vector Graphocephala atropunctata was tested. While the rpfF mutant was very poorly transmitted by vectors irrespective of whether they had also fed on plants infected with the wild-type strain, wild-type strains were not efficiently transmitted if vectors had fed on plants infected with the rpfF mutant. About 100-fewer cells of a wild-type strain attached to wings of a vector when suspended in xylem sap from plants infected with an rpfF mutant than in sap from uninfected grapes. The frequency of transmission of cells suspended in sap from plants that were infected by the rpfF mutant was also reduced over threefold. Wild-type cells suspended in a culture supernatant of an rpfF mutant also exhibited 10-fold less adherence to wings than when suspended in uninoculated culture media. A factor released into the xylem by rpfF mutants, and to a lesser extent by the wild-type strain, thus inhibits their attachment to, and thus transmission by, sharpshooter vectors and may also enable them to move more readily through host plants.

Replication of type 5 adenovirus promotes middle ear infection by Streptococcus pneumoniae in the chinchilla model of otitis media

PubMed Central

Murrah, Kyle A.; Turner, Roberta L.; Pang, Bing; Perez, Antonia C.; Reimche, Jennifer L.; King, Lauren B.; Wren, John; Gandhi, Uma; Swords, W. Edward; Ornelles, David A.

2015-01-01

Adenoviral infection is a major risk factor for otitis media. We hypothesized that adenovirus promotes bacterial ascension into the middle ear through the disruption of normal function in the Eustachian tubes due to inflammation-induced changes. An intranasal infection model of the chinchilla was used to test the ability of type 5 adenovirus to promote middle ear infection by Streptococcus pneumoniae. The hyperinflammatory adenovirus mutant dl327 and the nonreplicating adenovirus mutant H5wt300ΔpTP were used to test the role of inflammation and viral replication, respectively, in promotion of pneumococcal middle ear infection. Precedent infection with adenovirus resulted in a significantly greater incidence of middle ear disease by S. pneumoniae as compared to nonadenovirus infected animals. Infection with the adenovirus mutant dl327 induced a comparable degree of bacterial ascension into the middle ear as did infection with the wild-type virus. By contrast, infection with the nonreplicating adenovirus mutant H5wt300ΔpTP resulted in less extensive middle ear infection compared to the wild-type adenovirus. We conclude that viral replication is necessary for adenoviral-induced pneumococcal middle ear disease. PMID:25251686

Dominant negative mutant of ionotropic glutamate receptor subunit GluR3: implications for the role of a cysteine residue for its channel activity and pharmacological properties.

PubMed Central

Watase, K; Sekiguchi, M; Matsui, T A; Tagawa, Y; Wada, K

1997-01-01

We reported that a 33-amino-acid deletion (from tyrosine-715 to glycine-747) in a putative extracellular loop of GluR3 produced a mutant that exhibited dominant negative effects upon the functional expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors [Sekiguchi et al. (1994) J. Biol. Chem. 269, 14559-14565]. In this study, we searched for a key residue in the dominant negative effects to explore the mechanism and examined the role of the residue in the function of the AMPA receptor. We prepared 20 GluR3 mutants with amino acid substitutions within the 33-amino-acid-region, and dominant negative effects were tested electrophysiologically in Xenopus oocytes co-expressing the mutant and normal subunits. Among the mutants, only a GluR3 mutant in which an original cysteine (Cys)-722 was replaced by alanine exhibited a dominant negative effect comparable with that of the original mutant in which the entire 33-amino-acid segment is deleted. The co-expression of the Cys-722 mutant did not inhibit the translation of normal subunits in oocytes. The Cys-722 mutant formed a functional homomeric receptor with significantly higher affinity for glutamate or kainate than a homomeric GluR3 receptor. The Cys-722 mutation greatly enhanced the sensitivity of GluR3 for aniracetam, which alters kinetic properties of AMPA receptors. The kainate-induced currents in oocytes expressing the Cys-722 mutant alone showed strong inward rectification. These results suggest that the Cys-722 in GluR3 is important for dominant negative effects and plays a crucial role in the determination of pharmacological properties in AMPA receptor function. PMID:9065754

Characterization of CpSte11, a MAPKKK gene of Cryphonectria parasitica, and initial evidence of its involvement in the pheromone response pathway.

PubMed

Park, Jin-Ah; Kim, Jung-Mi; Park, Seung-Moon; Kim, Dae-Hyuk

2012-04-01

The gene CpSte11 of Cryphonectria parasitica, which encodes a yeast Ste11 homologue, was cloned and characterized. Gene replacement analysis revealed a high frequency of CpSte11 null mutants. When compared with the wild-type parent strain, CpSte11 null mutants showed no difference in terms of growth rate or pigmentation. However, CpSte11 null mutants showed a marked decrease in both the number and size of stromal pustules on chestnut twigs. The virulence test showed that, in comparison with those of the wild-type and virus-infected hypovirulent strains, CpSte11 null mutants produced necrotic areas of intermediate size. Disruption of the CpSte11 gene also resulted in defects in female fertility. Down-regulation of transcripts for the mating pheromone precursor gene, Mf2/2, and mating response transcription factors, such as cpst12 and pro1, was observed in CpSte11 null mutants. The down-regulation of Mf2/2, cpst12 and pro1 was also observed in the mutant phenotype of Cpmk2, a mating response Fus3-like mitogen-activated protein kinase (MAPK) gene, but not in the mutant of Cpmk1, a high-osmolarity glycerol Hog1-like MAPK gene. These results indicate that the cloned CpSte11 gene is functionally involved in the mating response pathway and acts through downstream targets, including Cpmk2, cpst12, pro1 and Mf2/2. However, the characteristics of the CpSte11 null mutant were fully phenocopied only in the cpst12 null mutant, but not in other studied null mutants of components of the putative mating response pathway. © 2011 THE AUTHORS. MOLECULAR PLANT PATHOLOGY © 2011 BSPP AND BLACKWELL PUBLISHING LTD.

SLC26A4 mutation testing for hearing loss associated with enlargement of the vestibular aqueduct

PubMed Central

Ito, Taku; Muskett, Julie; Chattaraj, Parna; Choi, Byung Yoon; Lee, Kyu Yup; Zalewski, Christopher K; King, Kelly A; Li, Xiangming; Wangemann, Philine; Shawker, Thomas; Brewer, Carmen C; Alper, Seth L; Griffith, Andrew J

2014-01-01

Pendred syndrome (PS) is characterized by autosomal recessive inheritance of goiter associated with a defect of iodide organification, hearing loss, enlargement of the vestibular aqueduct (EVA), and mutations of the SLC26A4 gene. However, not all EVA patients have PS or SLC26A4 mutations. Two mutant alleles of SLC26A4 are detected in ¼ of North American or European EVA populations, one mutant allele is detected in another ¼ of patient populations, and no mutations are detected in the other ½. The presence of two mutant alleles of SLC26A4 is associated with abnormal iodide organification, increased thyroid gland volume, increased severity of hearing loss, and bilateral EVA. The presence of a single mutant allele of SLC26A4 is associated with normal iodide organification, normal thyroid gland volume, less severe hearing loss and either bilateral or unilateral EVA. When other underlying correlations are accounted for, the presence of a cochlear malformation or the size of EVA does not have an effect on hearing thresholds. This is consistent with observations of an Slc26a4 mutant mouse model of EVA in which hearing loss is independent of endolymphatic hydrops or inner ear malformations. Segregation analyses of EVA in families suggest that the patients carrying one mutant allele of SLC26A4 have a second, undetected mutant allele of SLC26A4, and the probability of a sibling having EVA is consistent with its segregation as an autosomal recessive trait. Patients without any mutations are an etiologically heterogeneous group in which siblings have a lower probability of having EVA. SLC26A4 mutation testing can provide prognostic information to guide clinical surveillance and management, as well as the probability of EVA affecting a sibling. PMID:25960948